Immunodeficiency ailments. As well as primary immunodeficiency Primary immunodeficiency as a sign of classification pid

RCHRH (Republican Center for Development of Health Protection of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2015

D80.8) . 0), non-essential hypogammaglobulinemia (D80.1), Zagalny variable immunodeficiency, unspecified (D83.9), Zagalny variable immunodeficiency with important diseases in several cases).

Orpah zvoryuvannya, Pediatrics

General information

Short description

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expert joy
RSE on REM "Republic
center of development protect health "
Ministry of Health Protection
and social development
Republic of Kazakhstan
from "30" leaf fall 2015 to rock
protocol No. 18

value:

Classification

CLINICAL CLASSIFICATION (1):

diagnostics

Switching of the main and additional diagnostic entries:
The main (obov'yazkovy) diagnostics of the condition, which is carried out on an outpatient basis:
· Zagalny analysis of blood from a flared leucoformula;
· Zagalny analiz sechі;
Biochemistry analysis of blood: (the value of alaninaminotransferase, aspartate aminotransferase, zahalny bottle, zagalny and direct bilirubin, sechovine, creatine, glucose in the blood)

Dodatkovi diagnostics of the situation, which is carried out on an outpatient basis:
Immunoglobulin A, M, G.
· Blood analysis for VIL by the IFA method;
· Viznachennya group of blood and rhesus factor;
· Smears from infections;
Diagnostic fluorography of organs breast cancer(3 12 years) / oglyadovaya X-ray of the breast cancer.

A minimal change in obsozhennya, which is necessary to carry out when directed to a planned hospitalization: according to the internal regulations of the stationary with respect to the orderly order placed by the body in the health protection.

The main (ob'yazkovy) diagnostics, which are carried out at the stationary test at the advanced hospital and after the termination of terms in more than 10 days from the time of delivery of the analysis in accordance with additional instructions:
Determination of the main cell subpopulations of lymphocytes by the method of flow cytofluorimetry, (CD3 +, CD4 +, CD8 +, CD16 + / 56 +, CD19 +, CD20 +, CD3 + HLADR, CD3-HLADR), for the diagnosis B-lymphocytes;

Additional diagnostics, which are carried out at a stationary test at an emergency hospital and after the termination of terms for more than 10 days from the moment of delivery of analyzes in accordance with:
· Viznachennya ANA, RF, ANCA; C3, C4 complement bins for diagnostics of autoimmune acceleration.
· Preceding the titer of antigens to common antigens of the blood group (isohemagglyutinov);
· serological dosage blood for the detection of vaccine (pravets, diphtheria) antibodies for the development of a large decrease in any day;
For the value of the functional activity of lymphocytes - the value of the proliferative activity of T-lymphocytes along with the number of mitogens (- phytohemagglyutin) or bacterial antigens - in the low
Determination of phagocytic activity of leukocytes using differential diagnostics with other forms of PID:
· The number of neutrophils and monocytes is absolutely significant;
· Viznachennya phagocytosis, phagocytic activity.
· Oppressive dosage of all forms of PID for the detection of mutation (with the method of confirmation of diagnosis) of one or more gene.
· Post-mortem with trivial cytopenia, anemia, thrombocytopenia of unknown genesis, for the development of blood cells, reticular dizgenesis.
Gistologicheskie doslіdzhennya lymphatic universities- for the detection of dysplasia and germ-free centers (not developed at all), for the detection of abnormal cells, similar to those of Langerhans, T-lymphocytes and erythrocytes.
· Cultural pre-development of young loci and biological material on the emergence of an educator and assessment of his sensitivity to antibiotics;
· Advancement of biological material of local loci for the presence of pathogenic infectious microorganisms by the method of polymerase lanceolysis (PLR);
· Pre-treatment of blood cultures in case of stiff, trivial increased temperature of the body.

Diagnostic criteria for setting a diagnosis**:
Skargi and anamnesis.
skargi: On the bright side of the ear canal, showing a sludge on the mucus empty of the company, decreased appetite, blues, partly cold style, trivial cough, trivial temperature changes.
The adaptability of the scarg is dictated by the adaptability of the clinical manifestations of the accelerated PIDAV.
anamnesis:
· Renovation of a child at a visit to 1 rock at a vase and an adult;
· Post-vaccination acceleration (BCZhit desemination, polyomiulit paralytic and in.);
Transferred not less than 2 times of hypersensitivity, such as: meningitis (inflammation of the membrane of the brain), osteomyelitis (burning in the cells), celulite (burning of the child's blood), sepsis (systemic
· Parts of gnіynі otiti (fired vseredinі vuha) - not less than 3-4 times stretching one rock.
· Thrush is lax in children older than rock and fungal infection in children;
· fiercely hot sinuses nose (empty in the bones of the facial skull) 2 or more times stretching out to the rock;
· Recurrent gnіynі urazhennya shkіri;
· Recurrent types of bacterial infections of mental health, so that they oppose important forms, with the need for multiple courses of antibiotics (up to 2 months or more).
Oportunistic infections (Pneumocystic carini wikis), herpes group viruses, fungi.
Persistent viral infections, often, not to be cleared for a patient's viku:
a) for children of preschool age - 9 times and more,
b) for children of the school age - 5-6 times per day or more;
c) podlіtki - 3 - 4 times per rіk.
· Recurrent (repeated) diarrhea;
· Evidence of the attack and teleangiectasis;
· Greater lymphatic universities and spleen.
· Atopic dermatitis, enlargement, recurrent interruption without interruption;
· Emergence in the family of PID ailments;
Family history of the child's death early vik from the clinic to the infectious process;
Changes in the blood, such as: a decrease in the number of platelets (blood cells, which take part in the blood flow) - thrombocytopenia, a decrease in the number of blood cells (blood cells, which is a syndrome) umbilical wound, Melena, petechia on shkiri and mucous, ekhimosi, hematuria, nasal bleeding).

Physical details:
Dani ob'єktivnogo look:
· shkіra і pіdshkіrnі fabrics: poshkodzhennya hair structure / zubіv, ekzema, eritrodermіya novonarodzhenih, albіnіzm (chastkovy) blіda shkіra, netrimannya pіgmentu, distrofіya nіgtіv, shirokі condylomas / molluscs, vrodzhena alopetsіya, vіtіlіgo, petehії (rannіy rozvitok / hronіchnі) natechnіk, teleangіektazії, vіdsutnіst potovidіlennya;
· empty company: gingivostomatitis (important form), periodontitis, aphthae (recurrent), giant flares in the mouth empty, thrush, purchase of teeth, final growth, hypoplasia of the teeth, stiys;
· in the area of ​​eyes: ryzhennya sіtkіvki, teleangiectazії;
· estimation of parameters physical development: Decrease in vagi, adjusting to growth, disproportionate growth and growth.
Neurological signs:
· Ataxia;
· Microcephaly;
· Macrocephaly.
palpation:
· Visibility of lymphatic universities: sheepskin, groin, inguinal and migdaline.
Lymphadenopathy (nadmirna);
Asplenia, organomegaly (pechinka, spleenka).

Laboratory Doslidzhennya:
Zagalny blood analysis flaring, allowing the development of anemia, thrombocytopenia, leukopenia, hypereosinophilia, granulocytopenia or neutrophilia, lymphopenia:
· Vyavlennya Tilets Howell-Jolly (other round violet-chervoni included in the size of 1 - 2 microns, start by 1 (up to 2 - 3) in one erythrocyte. It represents an overflow of the kernel);
· Vyavlennya giant granules in phagocytes or the appearance of granules;
· Discovery of lymphocytes with basophilic cytoplasm;
Biochemical analysis of blood :
Zagalniy block і bіlkovі fractions - meaning a decrease in γ- fraction of globules on the electrophoregram of the zagalny bіlka, indicating the impaired synthesis of immunoglobulins
Viznachennya rіvnya calcium in blood, yogo reduction characterizes the hіpofunktsіyu parathyroid vinesі I will wash for the development of tetany.
· Viznachennya triglycerides, for the development of hyperlipidemia, in the power of ailments of the immune regulation (family hemophagocytic lymphogistiocytosis);
· Viznachennya feritin for differential diagnosis of hemophagocytic syndrome.
The value of the ignition reactions: CRP - a characteristic low level of CRP and other ignition parameters during an infectious process during PID
· The number of immunoglobulin A, M, G values ​​for the detection of a decrease (hypo-gammaglobulinemia) or an increase in daily activity (agammaglobulinemia).
· Viznachennya in the blood of immunoglobulin classes E (Ig E) with the sign of the appearance of the second significant change.

Immunologic blood count:
Table 1 - Immunological and genetic laboratory parameters for verification of PID form

Differential diagnosis

Differential diagnosis:
Algorithm 1 is to be amazed by the specification of the character of immunological breakdown.
Algorithm 2 is the most common type of immunodeficiency disease, genetic defects, and infection acceleration.

Malunok 2.

Likuvannya beyond the cordon

Take a lykuvannya in Korea, Izrail, Nimechchin, USA

Otrimati the consultation on medturism

lykuvannya

Cіlі lіkuvannya:
· Achievement of normalization of indicators of immune status and level of immunoglobulin;
Prevention infectious diseases;
· Early detection and treatment of infectious manifestations.

tactics of addiction:
· Dovichna change therapy (internal or secondary introduction of immunoglobulin). The internal introduction of immunoglobulin "G" is not common earlier. Pidshkirni immunoglobulins are given as an alternative to internal introduction;
· Lіkuvannya іnfektsіynyh accelerated - readily Protocols in the therapy of common nosologies. Prophylactic antibiotic therapy vikoristovuyutsya in case of lack of evidence for the optimal choice of immunoglobulin therapy;
· Lіkuvannya autoimmune and swollen pathology yak accelerated PID - vikoristovuyuvіdpovіdnі incapacitation of the protocol;
· Transplantation of hematopoietic cells with hyperimmunoglobulinemia "M".

Drug treatment

Table 2. drug therapy at new forms ah PID

preparations ( diyuchі speeches)

hospitalization

Indicated for hospitalization from the assigned type of hospitalization: Indicated for planned hospitalization:
· The first diagnosis in the presence of symptoms characteristic of PID;
· Carrying out a substitute therapy in / in immunoglobulins, at a time of day;
· Sharpening of recurrent gn_yno-igniting illnesses of broncholegenic systems, shkiri, ENT organs;
Autoimmunity accelerated development oncological illness on tli PID.

Indicated for the emergency hospital:
I will become, clutter up the life i get an urgent message medical aid: Hemorrhagic syndrome, heart-sudinna, dyshally deficiency, malignant fever.

prophylaxis

Prophylactic come in:
· Diet, every hour of the day, the syndrome of impaired moistening of children is not required. Diet is guilty of satisfying the need for bottles, vitamins and microelements, and to add calories to ensure normal growth and development. Lack of food for immunodeficiency can lead to an even greater impairment of immunity.
Children with relapsing chronic otitis media for early detection of deafness, regularly carry out additional hearing.
· Unique contact with sleepy radio.
· Monitoring of infection status. Sanation of chronic infections due to antibacterial therapy, anti-fungal and anti-inflammatory drugs.
· Before surgical or stomatologic entrances, the obligatory appointment of antibiotics for the prevention of infectious diseases is prescribed.
· Vaccine prophylaxis is not carried out vaccination with live vaccines (BCG, vaccination against bark, rubella, mumps, oral poliomyelitis, vitriana, rotavirus infection).
Vidmova from contacts with people, such as chills, vignettes of presence in the scenes of the great purchase

information

Dzherela and Literature

1. Protocols to send the Expert for the sake of RCHRH MHSD RK, 2015
   1. List of victorious literature: 1). I. V. Kondratenko, A. A. Bologov Primary immunodeficiency. M .: Medpraktika-M, 2005.2). Allergology and immunology. National Certification (Chief Editor of Academician RAS and RAMS Khaitov R.M., Prof. Ilyina N.I. 397 pp.). 1) Immunology childish vik(Ed. By Prof. A.Yu. Shcherbini and Prof. E.D. Pashanov) - М.: ID Medpraktika-mu, 2006, 432 p. 2) Drannik G.M. Clinical immunology and allergology. - К.: TOV "Polygraph plus", 2006. - 482 p. 3) Shcherbina A.Yu., Kosacheva T.G., Rumyantsev A.G. Primary immunodeficiency diseases: nutritional diagnosis and treatment // Nutrition of hematology, oncology and immunopathology in pediatrics. - 2010. - T. 9, No. 2. - S. 23-31. 4) Yartsev M.N., Yakovlev K.P. Immune deficiency: clinical and laboratory assessment of immunity in children // Immunology. - 2005. - T. 26, No. 1. - S. 36-44. 5) Kondratenko І.V., Litvina M.M., Reznik І.B., Yarilin A.A. Violation of T-cell immunity in ailments due to a foreign variable immune deficiency. Pediatrics, 2001; 4: 18-22. 6) Sidorenko I.V. Leshkevich I.A., Kondratenko I.V., Gomes L.A., Reznik І.B. "Diagnostics and treatment of primary immune deficiencies". Methodical recommendations for patients to the Health Protection Committee of the Moscow Uryad. M., 2000 .. 7) Khaitov R.M. physiology immune system... M., 2001., 223 p. 8. A.S.Yurasova, O.E. Paschenko, I.V.Sidorenko, I.V. Kondratenko Non-infectious manifestations of primary immunodeficiency. In the book. Successes of clinical immunology and allergology, 2002; 3: 59-79. 8) Effective pharmacotherapy 2012 rock number 1 side. 46-54.9) Rich Robert R. et all. Clinical Immunology. - 2008, Elsevier Limited. 10) Geha R.S. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee / RSGeha, LDNotarangelo, JLCasanova, H. Chapel, MEConley, A. Fischer, L. Hammarström, S. Nonoyama, HDOchs, JMPuck, C. Roifman , R. Seger, J. Wedgwood; International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee // J. Allergy Clin. Immunol. - 2007. - Vol. 120, No. 4. - P. 776-794.

information

List of rosters in the protocol:
1) Marshalkin Tetyana Vasilivna - candidate of medical sciences, doctor of the highest quality category, head of the department. folding somatic pathology and rehabilitation of the RSE on the RHV "NCP and DH".
2) Isabekova Alma Aytakhanovana - Candidate of Medical Sciences, Doctor of the Higher Qualitative Category, Department of Child Neurology with the Course of Medical Genetics, KazMUNO, Associate Professor.
3) Manzhuova Lyazat Nurbapaevna - candidate of medical sciences, doctor of the highest quality category of the head of the department of hematology, NCP and DH.
4) Bulegenova Minira Guseinovna - Doctor of Medical Sciences, Head. laboratory NCP і DH.
5) Gurtskaya Gulnar Marsovna - Candidate of Medical Sciences AT "Medical University Astana" Associate Professor of the Department of Foreign Pharmacology, Clinical Pharmacologist.

Ordering for the presence of a conflict of interest: dumb

reviewer:
Kovzel Olena Fedorivna - Doctor of Medical Sciences, head of the Department of Allergology, Pulmonology and Orfa Zahvoryuvan, Doctor of Allergology, Immunologist of the highest quality category of AT "Republican Center for Diagnostics."

Letting the minds look at the protocol: Revision of the protocol through 3 years of writing and publishing and from the date of joining the diya, or if new methods are evident with sufficient proof.

Attached files

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Immunodeficiency - a decrease in certain indicators and / or functional activity of the main components of the immune system, which leads to the destruction of the organism of the organism from pathogenic microorganisms and appears to be affected

As a matter of fact, the main function of the immunity system is the identification and elimination of alien speech of antigenic nature, so that it can penetrate into the body from the midst (microorganisms) or diagnose endogenously. This function is implemented for additional factors in congenital immunity (phagocytosis, anti-microbial peptides, protein systems and complement, NK-cell and in.) Regulation of the activity of components in the immune system of the organism and in their interaction with the search for additional cytokines and microcrystalline contacts.

In the cutaneous hyperactive components of the immune system, as well as in the mechanisms of regulation, there can be damage, which leads to the development of immunodeficiency, the main clinical manifestation of which is the increased sensitivity of the immune system. Rise 2 types of immunodeficiency: first and second.

primary immunodeficiency(ПІД) - decline, Encouraged by defects in genes, scho control of the immune response. ПІД - discomfort, developmental reasons for the nature and variety of immune defects, clinical manifestations and molecular damage. For a clinical picture of PID, it is characteristic of repeated and chronic, importantly against infectious processes, in the larger world of the bronchogenic system

і ENT organs, shkіri і mucous membranes; There may be development of gnіynі lymphadenitis, abscesses, osteomyelitis, menіngіt and sepsis. With deyakykh forms є show allergies, autoimmune disease and a powerful development of the evil chicks. Slid the beasts of respect for the return of the vital indicators of physical development. In a given hour, about 80 PID were described, genius emerged, leading to the development of a large number of diseases. Adequate laboratory analyzes allow differentiation of pathology on the basis of lymphocytes and pathology on the basis of non-lymphocytic mechanisms of destruction and development of antigens.

PID width to lay down from the form of a disease and in the middle to become from 1:10 000 to 1: 100 000 new people. Selective IgA deficiency, for example, develops on the basis of more often from 1: 500 to 1: 1500 of the foreign population. Extensiveness of the new forms of PID vary in the rural areas. Most often, there are defects in antibody production - 50-60% of vipads, combined PID - 10-30%, phagocytosis defects - 10-20%, complement defects - 1-6%. Greater PID is manifested in early childhood, if there are more and more pockets of PID forms, there is a growing variability of immunological deficiencies (cunny).

For the mechanism of development, there are 4 main groups of PID:

1st group - importantly humoral, or V-klіtinnі

ПІД;

Group 2 - combined PID (for all T-cell immunodeficiency disorders, impaired function of B-cell);

3-th group - PID, mumbled with defects in phagocytosis;

4th group - PID, accumulated with defects in the complement system.

Principles of diagnosis of primary immunodeficiency

An early diagnosis and an early ear of disease will begin to predict a disease. The statement of a diagnosis on the basis of clinical pediatric examinations is very difficult, but it is not very clear in the day-to-day possibility of a prompt consultation with a sick doctor-immunologist and a special laboratory immunological situation (Table 11). I would like to know the peculiarities of the classic picture PID і zradі

nya in zalnoklinichnyh laboratory analyzes allow to suspect PID and direct the sick person to fahivts. The European Immunodeficiency Suspension has broken down protocols for early diagnosis of PID, as well as the electronic database of the European PID registry. Algorithm for diagnostics of PID readings in Fig. 11-1.

Table 11-1. The stage of immunological treatment in case of adolescence for immunodeficiency

stage

method

Vivchennya іstorії ailments і physical examination, vimіryuvannya to maturity and vagi.

Viznachennya razgornoyu blood formula. Vimіryuvannya concentration of IgG, IgM and IgA і іх estimate according to vіku

Validation of specific results on control antigens (right, diphtheria).

Approvals for pneumococcal vaccine (for children 3 years and older). Analysis of IgG subclasses

Testing for specimens of candidiasis and pravtsya.

Discovery of lymphocytic surface markers: CD3, CD4, CD8, CD19, CD16, CD56.

Determination of lymphocyte proliferation (due to stimulation with mitogen and antigen).

Setting the reaction of a dical vibuch in neutrophils (as shown)

The value of the level of activity of the components of the system and the complement CH50 (external activity), C3, C4. Vimіryuvannya activityі of enzymes in adenosindezaminase and purine-nucleotide-phosphorylase of blood. Analysis of phagocytes (expression of superficial glucoproteins, decay, phagocytosis). Analysis of the level of cytotoxicity of NK-clitin. Analysis of the factors of the alternative activation system and complement - AH50.

Antigen testing for antigen (neoantigens) was not developed earlier.

The value of the superficial and intracytoplasmic molecules of cytin.

Vivification of the expression of cytokine receptors. Carrying out family / genetic dosages

Small. 11-1. Algorithm for diagnostics of primary immunodeficiency

The main features of the clinical picture of the first immunodeficiency

spend in classy paintings PID the so-called infectious syndrome - an increase in the absence of an infectious disease in general, innocently important recurrent (recurrent) The type of bud is determined by the nature of the immune defect. In case of defects in antibody production, infuse a stike up to antibacterial drugs flora - staphylococcus, streptococcus, hemophilous sticks. In case of T-cell immune deficiency, viruses appear (for example, the herpesvirus family), fungi (Candida spp., Aspergillusі ін.), and with phagocytic defects - staphylococcus, gram-negative bacteria, fungi, etc.

Laboratory dosage

As long as the critical data allow you to suspect the PID, then the next step is to carry out the following:

The definition of a flared blood formula (especially important indicators of lymphocytes are especially important);

The value of IgG, IgA and IgM in syrovatz blood;

Pidrachunok of T- and B-lymphocyte subpopulations;

For special shows:

◊ analysis of the functional stage of phagocytes (the most simple and informative analysis - test for the renewal of tetrazolium blue);

◊ analysis for the main components in the complement (repair from C3 and C4);

◊ analysis for VIL-infection (as well as possible factor risk);

◊ molecular-genetic dosage when indicated.

Principles of treatment of primary immunodeficiencies

The head meta therapy of PID is the treatment of accelerated disease and prevention. Tsey pidhid viklikaniy tim, scho defects of the immune system in case of PID laying on the genetic pry. In this hour, spend intensive training sessions on gene-

new therapy of immunodeficiency, which can lead to the emergence of more radical methods of treatment.

Falsely from the form of PID lykuvannya polyagaє in carried out the most effective therapy, treatment and prophylaxis of infectious, autoimmune manifestations of malaise, disease evil new creatures and the establishment of special methods, including the transplantation of hematopoietic stovburovicheskikh clitins (in the fallow type PID).

DEFECTS of immunoglobulin

Transient hypogamaglobulinemia in children

Transient hypogamaglobulinemia in children is associated with the physiological particularity of the phased formulation of the immunoglobulin system. In the greatest world, "remember" the dosage of IgM and IgA antibody formation. In healthy children, instead of maternal IgG, there is a stepwise decrease in the amount of viral IgG antibodies growing. In children, however, the growth of immunoglobulin rіvnya will be affected. Such children can suffer recurrent bacteria Infectious diseases... In cich vipads, it is not necessary to go into infusion preparations in donor immunoglobulins (introduction of intravenous immunoglobulin).

Selective immunoglobulin A deficiency

Selective immunoglobulin A deficiency (SD IgA - Selective Deficiency of IgA) develop as a result of a gene defect tnfrsf13b

abo p). IgA deficiency in the presence of immunoglobulin in the other classes is the most frequent immunodeficiency, which appears in the foreign population at a frequency of 1: 500-1500 people (in sick people who suffer from allergies), more often Deficiency of IgA is selectively identified, so that there is a deficiency in one of the subclasses (30% of the subclasses), and again (70% of the subclasses). Deficiency in IgA2 subclass should be produced to a greater degree of clinical picture, less deficiency in IgA1 subclass. There may be a diagnosis of IgA deficiency with minor impairments: with a defect in IgG biosynthesis and with abnormalities of T-lymphocytes. It is important to have a large number of particulars with selective

IgA deficiency is practically healthy. For children younger than 2 years, IgA deficiency is a physiological camp.

A decrease in the concentration of syrovatous IgA to<5 мг/дл у детей старше 4 лет; IgG и IgM в норме, количество и соотношение субпопуляций лимфоцитов и их функциональная активность могут быть в норме.

Klinichna picture. With IgA deficiency, 3 groups of pathological syndromes can develop: infectious, autoimmune and allergic. Patients with IgA deficiency are severe to recurrent infectious diseases of the upper secondary paths and organs of poisoning. Most frequent and importantly against anti-inflammatory autoimmune diseases, anti-inflammatory diseases (rheumatoid arthritis, ankylosing spondylitis, Sjogren's syndrome, vasculitis against damaged brain hemorrhages, autoimmune thyroid diseases, hyperthyroidism) The incidence of celiac disease changes in children with normal IgA 10 times. Allergic manifestations often occur: intolerance to a bottle of cow's milk, atopic dermatitis (ATD), bronchial asthma.

Likuvannya. Symptom-free symptoms do not affect any special treatment; in the presence of clinical manifestations of infectious, autoimmune and allergic diseases, carry out the treatment according to the standard.

The substitution of donor immunoglobulin therapy was not shown either in selective or in case of reversal IgA deficiency, or in cases of increased IgA deficiency.

Agammaglobulinemia with B-clitin deficiency

X-disease of agammaglobulinemia (Bruton's ailment) to become 90% of all types of agammaglobulinemia. Ailments lads, blue (אּ, ρ) carrying the defective gene btk (Xq21.3-q22), code specific for B-lymphocyte protein Btk (Bruton's tyrosine kinase- Tyrosine kinase Bruton). As a result of the defect, the destruction of internal signal paths, the recombination of important immunoglobulin lances,

rendering of pre B-cell in B-lymphocyte. In 10% of patients with agammaglobulinemia with B-cell deficiency, autosomal recession will settle down. 6 genetic defects have been described in this hour, including molecules of the pre-B-cell receptor, cytoplasmic. Leucine-Rich Repeat-Containing 8 (LRRC8).

Dani laboratory doslіdzhen. Peripheral B-lymphocytes are seen. Pre-B-cellin with μ-lance in the cytoplasm is present in the cystic marrow. The number of T-lymphocytes and functional test on T-lymphocytes can be normal. IgM and IgA in the blood cannot be injected; IgG can be present, albeit in small quantities (0.4-1.0 g / l). Hi antigens to antigens of blood groups and to vaccine antigens (right, diphtheria toxin and in.). Neutropenia may develop. Histological pre-development of lymphoid tissue: in lymphoid follicles of germ-native (germinal) centers and plasma cells.

Klinichna picture. If there is a family history of non-domia, then the diagnosis becomes obvious in the middle to the beginning of 3.5 years. For the incidence of the characteristic hypoplasia of lymphoid tissue, it is important to prevent the infection, infection of the upper (sinusitis, otitis) and the lower (bronchitis, pneumonia) of the mental illness; may gastroenteritis, pyoderma, septic arthritis (bacterial or chlamydia), septicemia, meningitis, encephalitis, osteomyelitis. Yak zbudnikiv getting sick Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, intestinal bacterium diarrhea abo lamblia Giardia lamblia. Patients with agammaglobulinemia are also sick to infectious diseases, mycoplasmas and ureaplasmas, which cause the development of chronic pneumonia, gnar arthritis, cystitis and abscesses. Among the types of neurotropic viruses ECHO-19 and coxsacks, which are both important hospitals, as well as chronic encephalitis and encephalomyelitis. Manifestations of intestinal infections can be dermatomyosis-like syndrome, ataxia, headache, and behavioral disorders. In sick children with a live polyvaccine immunization, as a rule, a trivial vision appears through the mucous membranes of the poliomyelitis virus, and due to the renewal of this deadline, a greater

there is a real risk of infection of healthy children with poliomyelitis as a result of contact with vaccinated immunodeficient children). Autoimmune disorders in agammaglobulinemia can be represented by rheumatoid arthritis, scleroderma-like syndrome, scleradema, nonspecific viral colitis, type I diabetes mellitus.

Physical look. I have a lot of respect for the appearance of physical development, for the shape of fingers (fingers for the eyes of drumsticks), changes in the shape of the breast, characteristic of the disease of lower mental health, for the hypoplasia of lymphatic

Likuvannya.

Zamisna therapy: intravenous immunoglobulin preparations should be administered dermally 3-4 times. Doses of immunoglobulins should be taken in such a way as to dissolve in syrovattsi ailing concentration, which will overcurve the lower boundary of the norm.

Discuss the potential of gene therapy - gene Btk cloning, prote yo hyperexpresis of the association from the evil transformation of the hematopoietic tissue.

At once on the easy neutropenia the growth factor is stagnant. When a sign of autoimmune pathology appears, it is possible to identify drugs in monoclonal antibodies (infliximab and in.).

Zagalny variable immune deficiency

Zagalnaya variable immune deficiency (cluny) is a group of syndromes, which are characterized by a defect in the synthesis of antibodies and immune deficiencies. A reliable diagnostic criterion of STODOL is the value of a decrease in the place of immunoglobulins in two or three main types in both of the articles in addition to one of the lower differentiated signs:

The debut of an affliction in the older than 2 years;

The prevalence of isohemagglyutinov and / or a low response to vaccination;

Viklyuchennya of the other causes of agammaglobulinemia.

For some ailments, the reason for the development of STODOL is mutations of genes, which code molecules, are obtained in the process of maturation and vivification B-clitin: BAFF-R (B-cell Activating Factor Receptor), Blimp-1 (B-lymphocyte induced maturation protein-1) i ICOS (Inducible costimulator). Defects in B-lymphocyte differentiation occur in plasma cells, defects in antibody production develop, and dysfunction of T-lymphocytes may occur, which makes it possible to develop mental retardation before they occur. The syndrome can manifest itself in early childhood, in adulthood, or in young people.

Dani laboratory doslіdzhen. Quite a decrease in the level of IgG and IgA (in about 50% of ailments) and IgM (right up to the amount of small amounts of disease). The number of B-lymphocytes in the blood appears to be normal or decreases. The number of T-lymphocytes in the majority of patients in the norm. In important ailments, lymphopenia develops (mensh 1500x10 3 cells in 1 liter of blood). The number of NK-clitins is reduced. Vibration of specific antibodies in response to immunization is reduced, for example, during the day. The proliferation of lymphocytes and the approval of IL-2 for the duration of mitogens and antigens are significantly damaged.

Klinichna picture. Recurrent bacterial infections occur due to localization, but also in the ecstatic paths and in the nasal sinuses. Until the moment of setting the diagnosis of infection of the dyshally nobles, it can progress to bronchiectasis and spreading of the lung tissue. Possibly infectious damage to the organs of poisoning, which can manifest itself in diarrhea, steatorrhea and malabsorption (and apparently the second mass). Often there are infections, wiklicans Giardia lamblia, Pneumocystis carinii for the viruses of the family Herpetoviridae. Ailments of the STODOL are sick to the development of severe arthritis, which is subject to mycoplasma and ureaplasma. Manifestations of enteral infections can be encephalomyelitis, polyemielito- and dermatomyositis-like syndromes, reduction of skin and mucous membranes. autoimmune getting sick is important and can start the forecast of the STANDOL. Some of the earliest clinical manifestations of STODOL: arthritis, nonspecific viral colitis and Crohn's ailment, sclerosing cholangitis, malabsorption, VCV, nephritis, myositis, autoimmune lesions of pneumonia in lymphocytic disease,

thrombocytopenic purpura, hemolytic anemia, pernicious anemia, total alopecia, vasculitis of the blood cells, photosensitivity. In STODOL ailments, the frequency (in 15% of cases) of sarcoidosis-like granules and non-malignant lymphoproliferation is significantly increased. Likuvannya.

Antibacterial chemotherapy.

Zamisna therapy: intravenous immunoglobulin preparations should be administered dermally 3-4 times.

In case of autoimmune acceleration - immunosuppressive therapy (glucocorticoids, azathioprine, cyclosporin A) and possibly prescribed drugs in monoclonal antibodies (infliximab and in.).

Hyper-IgM syndromes

Hyper-IgM-syndromes - to end up with rare illnesses, which are characterized by a decrease in the amount of IgG, IgA and normal or increased concentration of serum IgM. Cyclic shortage of lymphocytes in the presence of intermixing of immunoglobulin classes and hypermutagenesis of variable domains. Until the present hour, 6 genetic defects have been identified, which can be brought to the development of hyper-IgMcyndrome.

. Type 1 (HIGM 1). X-cell deficiency of CD40 lymphocytes (70% of the types of hyper-IgM-syndromes), so that T-cells are efficiently associated with B-lymphocytes.

. Type 2 (HIGM 2). Autosomal recessive, dressings with a defect AID - inductive activation cytidin deaminases (gene Aicda, 12p13)- the enzyme, which takes on the fate of the mixed classes of immunoglobulin and hypermutagenesis.

. Type 3 (HIGM 3). Autosomal recessive, linking with a gene mutation of the CD40 molecule. With a large number of B-cells, they do not themselves effectively interact with T-lymphocytes. Phenotypic manifestations are similar to those for type 1.

. Type 4 (HIGM 4). Autosomal recessive; in some cases of mutations are found de novo. Associated with a UNG defect - uracil-DNA-glycosylase - to the enzyme, possibly taking care of the fate

in the remixed classes of immunoglobulins, albeit written for the AID. In general, hypermutagenesis does not bump into the syndrome of contraction with a small vagina.

. Type 5 (HIGM 5). The defect is only in the overmixed classes, hypermutagenesis does not stick out. The causal mutation has not yet been revealed, but, obviously, a defect in the enzyme

AID.

. Type 6 (HIGM-ED). X-connections, associations with dyshidrotic ectodermal dysplasia, cyclic deficiency of NEMO (NF-kB modulator), which can lead to disruption of signal transmission from CD40.

X-lesions hyper-IgM syndrome see more often for others. It develops when there is a defect in the gene, but the code is CD40L (CD154, the gene for Xq26-q27.2)- ligand for CD40. Nedostatnіst ekspresії CD40L T-lіmfotsitami generally produces up nemozhlivostі peremikannya klasіv іmunoglobulіnіv in B-lіmfotsitah of IgM on INSHI іzotipi and torn down to takozh formuvannya B-klіtin pam'yatі, T i klіtinnogo repertoire of Th1-klіtinnoї vіdpovіdі, spryamovanogo proti vnutrіshnoklіtinnih mіkroorganіzmіv. lads ailing

Dani laboratory doslіdzhen. IgG, IgA, IgE do not stick out or appear in even small quantities. Rivn IgM in normal (in 50% of cases) or alterations, often significant. Number of T-and-B-clitin in the norm; decrease in the proliferative response of T-cellin, induction by antigens. IgM polyclonal, one monoclonal. Detect autoantitils of the IgM isotype (anti-hyperthyroidism, antiplatelet, anti-thyroid, antigen to antigens of smooth tissue). In lymphoid tissue, in the outer germinative center, in ale є plasmatic cells.

Klinichna picture. The first show up in a child and an early child. characteristic repetitions інфекції small localization (in the first place of the respiratory tract), including oportunistic (viclikan Pneumocystis carinii). It is also typical for viruses (cytomegalovirus and adenovirus), Criptococcus neoformans, mycoplasmas and mycobacteria. Cryptosporidial infection can be the cause of hostility and chronic diarrhea (developing in 50% of patients) and sclerosing cholangitis. Often develop anemia, neutropenia, mucus emptying of the company, gingivit, virazkov

urazhennya stravohodu, small intestinal malformations, nonspecific reddened colitis. Shine up to autoimmune distribution(Seronegative arthritis, glomerulonephritis, etc.) I malignant neoplasms (including lymphoid tissue, liver and bilious tract). Lymphadenopathy, hepato- and splenomegaly can develop. lykuvannya

Regular replacement therapy with internal immunoglobulin.

Antibacterial chemotherapy. For the prevention and treatment of pneumocystis pneumonia, take co-trimoxazole [sulfamethoxazole + trimethoprim] and pentamidine.

To improve the liver damage and the biological pathway, it is necessary to live only boiled or filtered water, to carry out regular cleaning (ultrasonic monitoring, biopsies of the liver are shown).

In case of elimination of neutropenia and an empty mouth, it is necessary to consume glucocorticoid preparations of granulocyte colony-stimulating factor.

With the development of autoimmune acceleration, immunosuppressive therapy (glucocorticoids, azathioprine, cyclosporin A), as well as preparations based on monoclonal antibodies, are prescribed.

The optimal method of treatment is the transplantation of the cystic marrow from HLA-sum donors (the survival rate is 68%, it is more efficient to carry out in vitro for up to 8 years).

COMBINOVANI IMUNODEFITSITI With an important defect in T-lymphocytes

Important combined immune deficiency

SCID (SCID - Severe Combined Immune Deficiency)- a group of syndromes, which are characterized by a decrease in the level of T-lymphocytes, or more often in the daytime and in impaired adaptive immunity. ... Reticular dysgenesis, which is characterized by deterioration in the maturity of lymphoid and early stages: neutropenia і T - B - NK -.

. X-linked SCID, develops as a result of gene mutation IL-2RG[(CD132, home at- receptor lance for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), Xq13.1-q21.1,אּ ], to lead to blockade of receptors and deficiencies of cell targets on the basis of specific interleukins (more than 50% of all types of TCIN); T - B + NK -.

. Lack of tyrosine kinase Janus3 [gene JAK3 (19p13.1),ρ ]; in case of gene defects, the transmission of the activation signal will be disrupted at-lantsyuga ІЛ-2, ІЛ-4, ІЛ-7, ІЛ-9, ІЛ-15, ІЛ-21 to the nucleus of the clitin, which should be used to make the differentiation of T- and NK-clitin to the breaking point; T - B + NK -.

. Lack of proteinintrosinphosphatase (CD45, gene PTPRC, 1q31-q32); in case of a gene defect, an increase in the Csk kinase activity on the Src protein and on the deterioration of the phosphorylation of the ITAM domains in TCR and BCR is increased; T - B + NK +.

. An additional deficiency of RAG1 and RAG2 enzymes, which activates recombination of V (D) J-segments in immunoglobulin and TCR [genes RAG1і RAG2 (11p13),ρ ]; T - B - NK +.

. Omen syndrome (incomplete deficiency of RAG1 enzymes and

RAG2) [geni RAG1 i / abo RAG2 (11p13-p12),R]. zavdyaki

low excess activity of the enzymes, all the development of a few clones of T-lymphocytes, specific to antigens of the epithelial tissues of the school and the herbal tract, when there are immunoglobulins in the first classes). Characterized by erythroderma and pachyderma with alopecia in the area of ​​the scalp and bruises, dyarrhea, which clogs the life with infectious syndrome; hepatosplenomegaly and hyperplasia of lymphatic universities.

. TKIN with increased sensitivity to ionizing radioactivity. Artemis nuclear cell defect [gene DCLRE1C, (10p),R], to enter the complex of enzymes necessary for DNA repair (take care of the part in the development of volunteers), with gene mutation, the V (D) J-recombination is damaged; T - B - NK +.

. IL-2 deficiency [gene IL-2, 4q26-q27].

Mutations of the IL-2 receptor a-lancyug gene (CD25) (10p15-p14);T - B + NK +.

Mutations of the IL-7 receptor a-lancyug gene (CD127) (5p13);T - B + NK +.

TAP deficiency (Transporter for Antigen Presentation), Necessary for the transport of antigenic peptides into the endoplasmic reticulum of the α-lancyuga receptor IL-7 (CD127) (5p13);T - B + NK +.

Mutations of genes of lancers CD3 (CD3γ, CDδ and CDε), which can lead to a decrease in the number of adult T-lymphocytes, a deterioration in differentiation; T - B + NK +.

Lack of protein ZAP-70 [gene ZAP-70 (2q12), R]. When the gene mutation inhibits phosphorylation of the ITAM domains of the ζ-lancer TCR and ITAM-receptors in the NK-clitin, selective deficiency of CD8 + T-clitin develops and proliferation).

Lack of adenosindezaminase [gene ada (20q12-q13.11 , p)], to produce up to accumulation in the cells of metabolites (deoxyadenozytriphosphate and S-adenosylgomocyteina), to reduce the proliferation of T- and B-lymphocytes (descriptions of options for capturing the debut) T - B - NK -.

Lack of purіnnucleosіdphosphorіlazi [gene pnp (14q11.2), p], to produce up to accumulation in cells of deoxyguanosine triphosphate, which inhibits the proliferation of T-lymphocytes (suppression syndromes - uricemia and uricuria); T - B + NK -.

Dani laboratory doslіdzhen. Evidence of variable, inodi glyboku lymphopenia; lymphocytes do not proliferate in response to a specific antigen; often a decrease in the level of immunoglobulins in syrovattsi blood is observed. On the roentgenogram of the thoracic cell, there is a thin thymus.

Klinichna picture. The name of the clinical diagnosis becomes obvious in the first 6 months of life, if the mother's IgG antibody is found. The most important paintings are on the first plan important infectious syndrome, Hypoplasia of lymphoid tissue and delivery to development. Infectious syndrome is characterized by oral candidiasis, chronic disease, pneumonia, fever,

sepsis of bacterial etiology, viral infections. Infectious diseases lie down to the other taxonomic groups: bacteria, viruses, fungi, intellectually pathogenic microorganisms (Pneumocystis carinii). Pneumonia often buva wiclicana P. carinii, diarrhea - by rotaviruses, Campylobacter, Giardia lamblia. Frequent manifestu viral hepatitis. Characteristic is the development of a regional or generalized BCZhit for vaccination.

lykuvannya transmission of signs of antimicrobial therapy, including parenteral administration, administration of intravenous immunoglobulin, antibiotics, anti-fungal and anti-external drugs. One of the main methods of treatment, which allows you to reach the end of your life, is the transplantation of the cystic marrow, without any child from TKIN, which, as a rule, will die on the 1st life. Described by one vipad, if the child in especially sanuvati minds lived up to 2-3 years. It is important to develop SCID in newborns earlier, as it is fatal for them, for example, immunization with live vaccines. Immediately for the diagnosis of such children, it is necessary to put them in a gnotobiological mind (sterile box). In case of admission of infectious diseases, to carry out intensive anti-bacterial, anti-fungal and anti-fungal therapy, replace therapy with internal immunoglobulin. For the prevention of pneumocystis pneumonia, co-trimoxazole should be used. In order to develop BCZhit, it is necessary to carry out a trivial intensive anti-tuberculous therapy. For the transfusion of blood components, you need to use only the optimized and refined preparations. Є risky development of post-transfusion reaction “graft against the sovereign” in connection with transplacental transfer of maternal lymphocytes.

Naked lymphocyte syndrome

This is the name of the pathology, if the organism does not express the MHC-I or MHC-II molecules. For the duration of the expression of MHC-I molecules, there is a decrease in CD8 + T-lymphocytes versus the daily activity of NK-clitin; at the time of the MHC-II decrease in the CD4 + T-lymphocyte level. A number of genetic defects have been characterized. However, the defects are not localized in the MHC genes, but in decile factors that are indicative of the regulation of

express. key picture syndrome of "naked" lymphocytes i lykuvannya analogous to those with other SCID.

Dijordzhio syndrome

With Dijordzhio syndrome, or syndrome defect of the third and fourth pharyngeal intestines [deletions in 22q11, including the gene TBX1 (22q11.2), diagnose hypoplasia, such as thymus aplasia, parathyroid hypoplasia, wadi heart, deficiency of T-lymphocytes, variable amounts of B-lymphocytes.

Dani laboratory doslіdzhen. The value of the decrease in the number of CD3 +, CD4 + and CD8 + T-cellin and the decrease in the proliferative activity, induced by mitogens and antigens. Amount of B- and NK-clitin in the norm. Concentration of syrovatous immunoglobulin in a large amount in between norms, there may be different variants of dysgammaglobulinemia.

Klinichna picture. The immunodeficiency component of the hypoplastic or aplastic thymus presentation is recurrent, it is important to avoid Infectious diseases. There is also hypo-parathyroidism (hypocalcemia, as a result, - tetany, I will remember it on the 1st or 2nd day of the population); malformations of the circulatory system (right rotation of the aortic arch, stenosis of the right slunker, defects in the mid-slurry and the anterior septa, Fallot's tetrad, atresia or hypoplasia of the legacy artery); depression of the day; anomalies of the facial skeleton (increased appearance between the young organs, slits of reduced size, especially the lower, low-set in the shell, short tray groove). Violations of anomalies of the larynx, pharynx, trachea, internal vuh, stravohode; impaired development of nirok, central nervous system and other malformations of development (polydactyly, visibility of nigtins, atresia of the anus, anal fistula). Characterized by the overlap of motive and psychomotor development. I mean the ability to autoimmune distribution(Cytopenia, autoimmune thyroiditis) and malignant neoplasms.

Likuvannya.... Antibacterial and anti-virus therapy. ... Replacement therapy with intravenous immunoglobulin preparations. ... Hirurgichesky lіkuvannya with the method of corrections vad development. ... With autoimmune acceleration - immunosuppressive therapy. ... If endocrinopathies are evident, correction of endocrinopathies is observed. ... Cell transplantation is not effective

tivna. ... The transplantation of the epithelial tissue of the thymus is justified. Correction of the function of parathyroid vines.

X-lesions lymphoproliferative syndrome

NS- lymphoproliferative syndrome is characterized by impairment of the immune response to the Epstein-Barr virus [accumulation of gene defects SH2D1A(SAP) in Xq25,אּ], to produce uncontrolled proliferation of B lymphocytes transformed by the Epstein-Barr virus, and infecting new target cells with the virus.

Klinichna picture. Described 4 most widespread phenotypes: important infectious mononucleosis, malignant lymphoproliferative disease (lymphocytic leukemia, importantly B-cell), anemia and pancytopenia (in this number, the syndrome Inflammation of the Epstein-Barr virus is a critical (triggering) mechanism of the formation of the most important, rapidly progressive and fatal illness: fulminant infectious mononucleosis (in 58% of the adolescents to an adolescent syndrome of up to 100 years) In 10% of vipads, the phenotype manifests itself before the infection with the Epstein-Barr virus (at which, as a rule, dysgammaglobulinemia and lymphomy develop). Naybilsh often show different types of hypogammaglobulinemia. To produce immunodeficiency to the development of bacterial, fungal and viral Infectious diseases. The transmission of an illness is possible in boys with a characteristic family history and a positive PLR-positive test for the Epstein-Barr virus. For diagnostics, it is recommended to vikoristovuvati after a genetic analysis SH2D1A and estimates from the SAP Expression.

lykuvannya

With the help of prophylaxis, it is recommended to vikoristovuvati anti-virus drugs - acyclovir, valacyclovir (іх early sign of attracting a replication of the Epstein-Barr virus in the mouth)

In case of hypogammaglobulinemia, intravenous immunoglobulin shomyatsya should be used in conjunction with antibacterial therapy.

For the elimination of fulminant infectious mononucleosis, high doses of acyclovir and methylprednizolone, high dose therapy with internal immunoglobulin with a high titer of antibodies to the Epshtein-Barr virus are used.

With the development of hemophagocytic syndrome, take a high dose of dexamethasone s Vepesid ♠ (etoposide).

In the case of malignant illnesses, use the standard protocols of therapy.

A radical method of treatment is cystic marrow transplantation from HLA-sum donors.

Autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome - a group of sickness, which is characterized by good lymphoproliferative defects, hyperimmunoglobulinemia, autoimmune disorders, with a subtype of blood CD3 + CD4 - CD8 - Fas(CD95) - TNFRSF6 (10q24.1), gene caspase-10, Fas-liganda - FasL (1q23)].

Dani laboratory doslіdzhen. Zmist CD3 + CD4 - CD8 - T-lymphocytes in peripheral blood or in lymphoid tissues become more than 1%. Rivn IgG, IgA and IgM can be normal, increase or decrease. In addition, hypergamaglobulinemia is reduced to a low concentration of syrovatous immunoglobulin, right up to agammaglobulinemia. Vyavlyayut autoantitil to erythrocytes, thrombocytes, neutrophils, smooth ointments, to factor VIII; antinuclear and antiphospholipid autoantitila, as well as rheumatoid factor and іn. Characteristic lymphocytosis.

Klinichna picture. All the ailments have improved ovens, lymph universities (in the first 5 years of life) and spleens. Lymphoproliferation does not lead to changes in temperature and low temperature conditions. debut autoimmune reactions You may not be able to get rid of lymphoproliferation and infusion. Due to the severity of autoimmune reactions of the build-up. Autoimmune reactions against blood cells (hemolytic anemia, thrombocytopenia, neutropenia) develop more often, and the more often these organisms are consumed. Additions to the development of malignant new diseases (T- and B-lymphoid, Berkitt's lymphoid, atypical lymphoid, lymphogranulomatosis, etc.).

Likuvannya.... Chemotherapy drugs (cyclophosphamide, azathioprine, methotrexate, chlorambucil). ... Glucocorticoids. ... Splenectomy with advanced hypersplenism and hemocytopenia. ... In important cases, cystic marrow transplantation is possible.

Hyperimmunoglobulinemia E syndrome

Hyper-IgE-syndrome is characterized by hundreds of changes in serum IgE, repeated abscesses of the skin and pediatric cells of the staphylococcal etiology, pneumonia with the form of pneumocele, anomalies of the skeletal disorders of the face. The molecular-genetic nature of the hyper-IgE syndrome has not been established until cich pyr. In some cases, an autosomal dominant is revealed, in others - an autosomal recessive decline. Allowing for defects to receive signal molecules of cytokine receptors (in the autosomal dominant form of the syndrome, even in the presence of mutations in Stat3) and, possibly, tied to the broken function of the Th17-clitin subpopulation. The other gene, which is indicative of the formation of hyper-IgE syndrome, is localized on chromosome 4 (4q).

Dani laboratory doslіdzhen. Detection of developmental immunological damage: adjustment of IgE levels in syrovatics, failure of neutrophil chemotaxis, defect of detection of antibodies; a decrease in the reaction of HRT to candidin, diphtheritic and pravtsevium toxoid; weakening of the proliferative activity of T-clitin in Candida and pravtsevy toxoid in case of sparing the appearance of mytogenicity. Eosinophilia in the peripheral blood and in the lineage of small abscesses. Quantity of T-and-B-clinical in the norm.

Klinichna picture. Eczema of moderately severe disease in the early age. Characteristics of the appearance of the face (wider, wide brick, asymmetry of the facial skeleton, like a prominent forehead, deeply planted eyes, a high palate). There are anomalies in the development of the skeleton, scoliosis, increased looseness of loam, stiffness to fracture of the cysts for minor injuries, damage to teeth. There are abscesses in schools, pediatric cells and lymphatic universities. Pneumonia develops in a larger senior vice (most part of the S. aureusі H. in-

fluenzae), in 77% of cases a pneumocele is formed, infection is present, P. aeruginosaі A. fumigatus. Pneumonia can occur without temperature adjustment. Chronic candidiasis of mucous membranes and nigtiv develops in 83% of cases.

Likuvannya.... Triva (with the help of prophylaxis - previchna) antibacterial and anti-fungal therapy. ... For the treatment of dermatitis, topical conditions are stagnant, in important cases - low doses of cyclosporine A. Cystic marrow transplantation is ineffective.

CHROMOSOME BREAKING SYNDROME

For syndromes with chromosomal instability: AttacksTeleangiectasia[Defect of the DNA-topoisomerase gene ATM (11q22), p] i Nijmegen syndrome[Defect of the nibrina gene NBS1(8q21)] - the characteristic frequency of malignant puffins, spontaneous chromosomal instability and chromosomal breakage is increased. The offense of the baby takes a part in the repair of double-stranded DNA changes and regulation of the cell cycle. In the norm, double-strand DNA breakdown occurs in the process of V (D) J recombination of immunoglobulin and TCR genes, intermixed immunoglobulin classes, for an hour crossing over during meiosis. Similar processes occur when neurons in the brain are ripened. Defects in DNA repair in ataxis-teleangiectasis and Nijmegen syndrome add to such clinical manifestations, such as disrupting the synthesis of immunoglobulins, the function of state organs and the nervous system.

Ataxia-teleangiectasia

Tsey syndrome (frequency 1: 300 yew. Newcomers) with a heterogeneous phenotype was described by the French licar D. Luy-Bar. Symptoms of ataxia can occur in a child even in 2-4 months. The ataxia was accompanied by the progressive degeneration of purkin's clitin into the corns. Teleangiectasis on the nasal ridges, in the shells, on the conjunctiva appear cheaply, up to 3-6 rockets. Often on shkіrі they are called "kawi with milk."

There is a type of clinical symptomatology. Reduced number and functional activity of T-clitin (mainly CD4 + T-clitin). The initial number of T-lymphocytes in the majority of normal patients. Supravularly temporarily (200 times in vische, lower in the out-of-town population) the frequency of neoplasms (including lymphomas and carcinomas), it is not easy to produce a lethal result of up to 10-12 years. lykuvannya symptomatic.

Nijmegen syndrome

Syndrome Nijmegen (for the name of the place in Holland, deceased for the first time described a disease) manifests itself as microcephalus, specific damage to the facial skeleton (bending of the forehead, as the middle part of the face, great nis, hypochondylitis) development, the appearance of the beaches "kawi with milk" on skіrі; clinodactyly and syndactyly, dysgenesis of women and in. Most children suffer from recurrent and chronic bacterial Infectious diseases dikhalnyh nobles, ENT organs and the secular system. In 50% of vypadkіv develop malignant new solutions, more importantly In-klinnі lіmphomi. The development of dysgammaglobulinemia, a decrease in CD4 + T-clitin.

Likuvannya.... Symptomatic therapy of neurological disorders. ... Replacement therapy with internal immunoglobulin. ... Antibacterial, anti-tress, anti-fungal therapy should be used for patients. ... In case of bad taste, the new solution will increase the sensitivity to radioactivity and chemotherapy.

Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome [gene defect WASP (Xp11.23p11.22),אּ; also ρ і Ʀ] Gen WASP(from Wiskott-Aldrich syndrome) It is expressed in lymphocytes, tissue, spleen and thymocytes. Mutations of the associased gene with abnormal expression in neutrophils and T-lymphocytes (CD4 and CD8) of the CD43 molecule (a ligand for ICAM-1, demonstrates antiadhesive function).

Dani laboratory doslіdzhen. Thrombocytopenia (less than 10% of the norm) is accumulated by the increase in the rate of blood cells.

Thrombocytes are of lesser size, less in healthy people. The level of IgM in syrovattsi blood decreases with a normal level of IgG and increased versus IgA and IgE. The titers of isohemagglyutinins are reduced, the setting of antibodies to polysaccharide antigens of pneumococcus, streptococcus, intestinal bacillus, salmonella, as well as anti-foreign antigens is reduced. At an early age, as a rule, the number of lymphocytes is normal, with 6 levels of lymphopenia (less than 1x10 9 / l), a decrease in CD3 + and CD4 + T-clitin with a normal level of B- and NK-clitin. Possible eosinophilia and development of posthemorrhagic anemia. The proliferative response of T-clitin to mitogen and antigen decreases, HRT is weakened. In the normal structure of germ-natal centers and T-cells, they do not appear in the normal structures.

Klinichna picture. An affliction is characterized by a triad of signs: thrombocytopenia, eczema and recurrent infectious diseases. Hemorrhagic syndrome manifests itself early, even during the neonatal period (petechial visipus, cephalohematomas, bleeding from the umbilical wound, intestinal bleeding). Eczema manifests itself early in 80% of ailments. In addition, signs of immunodeficiency build up: bacterial infections of ENT organs, mental systems, etching organs, shkiri; expanded or generalized herpetic infection (Herpes simplexі Varicella zoster), cytomegalovirus, as well as fungi (candidiasis of mucous membranes), earlier oportunistic infections. In 70% of ailments, autoimmune disease (hemolytic anemia, neutropenia, arthritis, insidious vasculitis, nonspecific inflammatory colitis, cerebral vasculitis, glomerulonephritis, autoimmune) In patients older than 5 years, the frequency is increased evil new creatures(More importantly, fluffy lymph fabric).

Likuvannya.... Transplantation of allogeneic cystic marrow with abnormal cells (the success rate of the operation reaches 90% in the case of vicious transplant from the donor's histological content and 50% in the case of haploid transplantation). ... Replacement therapy with internal immunoglobulin. ... Prophylactic signs of antibacterial, anti-fungal and anti-tine drugs. ... To change the hemorrhagic syndrome, splenectomy should be performed. ... In case of autoimmune acceleration, immunosuppressive therapy is indicated.

DEFECTS phagocytosis

Chronic granulomatous ailment

Chronic granulomatous ailments are characterized by impairment of the functional activity of phagocytes (establishment of active forms of acid radicals, intracrystalline killing and fragmentation of phagocytic pathogens), permanent bacterial fungal infections. Chronic granulomatous ailments develop in particular with genetic defects [in 65% of cases - X-type diseases of the disease: gene gp91-phox (Xp21.1),אּ; in 35% of cases - autosomal recessive: gene f47-phox (7q11.23),ρ; gene p67-phox (1q25),ρ; gene p22-phox (16q24), p], which leads to damage in the NADP-oxidase system. When the short-lived (kilka years) neutrophils of the non-beaten bacterium are bent, they are "viplivayut" in the fire. Macrophages are still living cells, and their alternates (monocytes) play in the head in the growing number granulomi), they phagocytize microorganisms, but don't drive them in.

Dani laboratory doslіdzhen. Characteristics of normal values ​​of syrovatous immunoglobulins and subpopulations of lymphocytes. Osvita of peroxide radicals by neutrophils, assessed in tests (luminescent chemiluminescence or renewal of tetrazolium blue), sharply reductions in general. At the same time, infectious diseases are characterized by leukocytosis, neutrophilosis, anemia, anemia, hypergamaglobulinemia.

Klinichna picture. Inspiration in a large number of vipadkiv appear on the first occasion of life infectious syndrome(Infections of internal and post-occlusive pathogens) and granules. Most types: lesions (recurrent pneumonia, lesions of root lymph nodes, abscesses of legends, lesions of pleurisy), herbal tract, shkirni abscesses and lesions. Most of the pupils - catalase-positive microorganisms: S. aureus, Aspergillus spp., intestinal gram-negative bacteria (E. coli, Salmonella spp., Serratia marcescens), more - Burkholderia cepaciaі Nocardia farcinica. Characterized by the development of pechinkovy and subphrenic abscesses, osteomyelitis, pararectal abscesses, sepsis.

Nayvazhche, life-threatening infections are not accelerated - aspergilosis, which can prevent diffuse lesions and other organs (adipose cells, brain, cysts, lobes, endocardium). In patients with chronic granulomatous ailments after BCG vaccination, vaccine assays of infections often develop, and regional lymph nodes are obtained. Mycobacterium lesions in ailments on chronic granulomatous ailments can occur as Legeny, as well as lateral localization and wear a prolonged interruption. For ailments with chronic granulomatous ailments, it is characteristic of the appearance of physical development.

Likuvannya.... Anti-microbial therapy: preventive maintenance of co-trimoxazole and anti-fungal drugs (іraconazole and іn.); in case of diagnosed infectious diseases, parenteral administration of combined antibacterial therapy (2-3 bactericidal antibiotics, which penetrate internally) is carried out in conjunction with anti-fungal therapy. With the development of aspergilosis, it is shown to trivially consume amphotericin B or caspofungin. When MAC is infectious, it is necessary to use a combination of trivial specific therapy with anti-tuberculous drugs with antibiotics of a wide spectrum of diy. ... Surgical treatment is often superseded by suppurations of operational wounds and the formation of new wars. You can punctuate the abscess under ultrasound control. ... For the treatment of important infectious diseases in case of non-efficacy of antibacterial therapy, it is possible to treat granulocyte mass, high doses of IFNu and G-CSF. ... Cystic marrow transplantation, or transplantation of umbilical cord blood cells from sumy sibling, can be successful in the early years, since there is a minimal risk of death due to the infection of the hospital's delayed transplant and reactions.

Leukocyte adhesion defects

On the current day, 3 leukocyte adhesion defects were described. All the stench may be

autosomal recessive type of decline, characterized by repeated and chronic bacterial and fungal infections. Type I is characterized by a decrease in the expression of CD11 / CD18 on leukocytes, impairment of neutrophil chemotaxis, leukocytosis (more than 25x10 9), a decrease in the decrease in the umbilical cord penetration and growth

Likuvannya.... Antibacterial therapy: infectious diseases and prophylactic. ... In case of severe interruption, the transplantation of the cystic marrow from an HLA-sum donor is considered.

DEFECTS of the system and complement

Ailments with deficiency of complement components

Show genetic defects in the peripheral components of the systems and in the complement of the induction in the table. 11-2.

Spadkovy AT. Ailments, accumulated with a deficiency of components in the complement, appear rather rarely, for the manifestation it is necessary to have a homozygous stance for autosomal alleles. Є One vignatok, tied with C1inh (ingibitor C1-esterasi): gene mutation C1inh, as a result of a deficiency of an ingibitor, in a heterozygous state it manifests itself as a phenotype, we see it as a fall-off AT (div.

Ailments of immune complexes. Lack of C1-C4 is manifested by the development of ailments of immune complexes - systemic vasculature and nyrok, which is commonly called systemic worm-like syndrome (VVC).

Pіogennі іnfektsії. Deficiency of C3 (also factors H and I) of associations with an increase in dryness to infectious diseases. Deficiency of components, how to take part in the alternative path of activation of complement, as well as deficiency of components C5-C8, as Neisseria spp. C9 deficiency is clinically asymptomatic.

Table 11-2. Clinically show defects in the peripheral components of the system and in the complement

Ingredinti

Klinichny show

C1q, 1p34.1, R

Bacterial infections, VKV with glomerulonephritis

C1r, 12p13, R

Bacteriological infections, VKV

C4, 6p21.3, R

the same

C2, 6p21.3, R

Bacterial infections, VKV in 15% of patients

C3, 19, R

Factor D, Ʀ

Infection due to Neisseria spp.

Factor P (properdin): Xr11.23, R

the same

factor H

Pyogenic infections, VKV with glomerulonephritis

factor I

To f

C5, 9q32-9q34, R

Infection due to Neisseria spp.

C6, 5h, R

To f

C7, 5h, p

To f

C8, 1p34-α , β, 9q-γ, ρ

To f

C9, 5p13, R

squeak asymptomatically

C1inh (ingibitor C1 component to complement), 11р11.2-11q13,Ʀ

slumpy AT

DAF, 1q32.2

Hemolysis with paroxysmal low hemoglobinuria

CD59

the same

pіogennі іnfektsії

* - including gene, decline.

Lectin deficiency causing manosis

Lectin deficiency, which is associated with manosis (name: mannans-binding lectin - MSL), accumulation of a gene defect MBL(The number of points of mutations and deletions in the gene MBL appear in 17% of people of the European race). In case of gene defects, the activation of proteases is disrupted, so the components of the complement C2 and C4, and the activation of the system and the complement along the lectin path, are broken. classically tsya pathology is manifested by infectious syndrome.

Dani laboratory doslіdzhen. The analysis of subpopulations of lymphocytes, leukocytes, and also the types of immunoglobulins does not indicate the majority of diseases, adequate clinical symptoms. At the syrovatz blood of the main MSL.

Likuvannya. Tse become ill with not є classic immunodeficiency. Otzhe, immunocorrection mіzh structure by means of different indications. Recombinant MSL can be used as a pharmacological drug for etiopathogenetic therapy for patients with cystic defect. In a given hour, the drug undergoes clinical testing.

The immune system of people is designed to quickly react to the invasion of alien elements. Correct її functionality - the process of designation of contamination and її property. Primary immunodeficiency means that the child does not have a formulated mechanism with intrauterine development, for not having taken it off according to a decongestant official. As a result, if you use microorganisms in your body, you will bring you maximum performance. The same can be said about atypical cells, how to repair negative influx on the health camp, to wick the pathology of seriousness.

Slid development of primary and secondary immunodeficiency. The first viznachatsya at nemovlyati nebarom writing people. Yogo organism of amusement of power is captured from antigens, schilny before infectious invasion. It’s because of the fact that the little one is often ill, that he can add up to repeated ailments, it’s important to endure it, we’ll take it away. The important form of the primary immunodeficiency is produced before death in the child.

As a result of childbirth, if the primary immune deficiency was manifested in older adults. So it is possible, but for all people, people are guilty of being able to compensate for the singular ailment.

Klіnіka zhvoryuvannya - tse re-information, the transition of the ailment into a chronic form. Why to produce a pervinny immunodeficiency:

1. Patient suffering from bronchogenic anomalies.
2. At a new level, mucous membranes and shkirny curvatures.
3. Є problems with ENT organs.
4. PIDS, as a rule, lead to lymphadenitis, abscess, osteomyelitis, meningitis, sepsis.
5. Singing forms of primary immunodeficiency provoke allergies, autoimmune illnesses, growth of malignant new diseases.

Investigation of the deterioration of the functions of the immune system to the immune system is to be engaged in immunology - the science of the development and formation of the immune mechanism, against the penetration of antigens into the body and the knowledge of schooling organisms with the help of microorganisms.

If the IDS is diagnosed earlier, the child has more chances to see and develop life from a healthy body. More important is the value of a timely genetic mutation, as it gives the opportunity to benefit from the plans of the family.

Immunodeficiency is a factor of an anomaly in the mechanism of immunodeficiency, as it gives rise to immunodeficiency in the immune response to the injection of antigens. Tsei zb_y can be chotir'oh vid_v:

• vikovoi, tobto vinyk in a child, or in a kidnapped vіtsі;
• embankment through the wrong food, the way of life, the way of life, the way of life, the virus SNID, etc.;
• having developed as a result of new infections;
• vrodzheniy abo pervinny VD.

PIDS is classified as fallow in the form and severity of the disease. Prior to primary immunodeficiencies, the following are reported:

• VD is characterized by the rate of decilkokh clitinnyh complexes;
• Dysgenesis of the reticular, when stovbrovі klіtini vіdsutnі, tse prirіkє of the newly born to death.
• An important combination of VD is the decline in sickness, dysfunction in T-lymphocytes.
• George's Syndrome - abnormalities of the thymus, parathyroid glands - underperformance, or the appearance of the thymus. As a result of the defect, T-lymphocytes are observed, congenital heart disease, deformities in the cyst structures, facial cysts, nircovy defects and dysfunction of the central nervous system.
• Primary immunodeficiency, accumulation of B-lymphocytes.
• Damage in small cells, which provokes chronic granulomatous ailments (CGD) with anomalies in sour exchange. A defect in the activation of active sour sensitive fungi and bacterial infections.
• Defects of folding blood cells, which can destroy humoral zakist. In the complement system, there can be a daily number of warehouses.

Needed for the nobility! Clinical immunodeficiency is characterized by a lack of immunocompetent cells, including lymphocytes, plasma cells, macrophages. Humoral immunodeficiency means dysfunction in viral antibodies.

Symptoms of primary immunodeficiency

On the first signs of immunodeficiency, symptoms will show that symptoms. Vivchayuchi klinichnu picture of the prevention of ailments, lykary klinika vyavlyayut a type of immune deficiency. Tsyom spriyє look around, analysis, anamnesis for the determination of genetic pathology.

1. The primary deficiency of the immune system is caused by the infection of the viral and fungal character. The characteristic signs are repeated chills, the importance of GDVI contraction, varicose veins, parotitis, and some herpes. Ailment suffers from thrush, inflamed legends, organs in the intestinal tract, accumulated with fungi. Clinical immunodeficiency in patients with advanced oncology, lymphomy.
2. Lack of humoral infection to provoke bacterial infection. Tse pneumonia, gn_yniki on shkіrі, erysipelas, staphylococcus, streptococcus.
3. Lack of level of secretory immunoglobulin A infection of mucous membranes in mouth, nose, eyes, intestines, bronchi.
4. Combined VD are characterized by accelerated external and bacterial infections. Manifest the form of primary immunodeficiency is nonspecific - the stench rotates in vices of development, swollen processes, lymphoid tissues, thymus, megaloblastic anemia.
5. Prognosis of neutropenia and dysfunction of phagocytosis of granulocytes is caused by bacterial ignition processes with gnarines, abscesses. The result may be sepsis.
6. Complement-assotiation of primary immunodeficiencies to pull bacterial infections, autoimmune diseases, as well as recurrent swellings on children, children - recessive angioedema.

Causes of primary immunodeficiency

Dysfunctions of the immune system are formed in the embryo in the middle of the mother's womb. Riznі officials are pouring into the process. Prenatal diagnostics showing the development of a fetus with immunodeficiency. Ethiology PIDS primed on three pathologies.

1. Genetic mutations, which mean, in genes, such as those found in the immunocompetent clientele of their functions, are seen by snakes. To break down the process of development and differentiation of clients. Decline of anomalies in an autosomal recessive type, if both are mutagenic. It is only insignificant that the number of mutations develop spontaneously or in a germinative way (in articles).
2. Teratogenic factor - the whole infusion of non-safe toxins on the membrane, which can lead to ugly primary immunodeficiency. Provoke VD TORCH-infections - cytomegalovirus, herpes, rubella, toxoplasmosis in vaginal women.
3. Unclear ethology. Immune deficiency, the reason for which is not clear.

Prior to such conditions, there are no symptoms of VD, which are manifested in infectious accelerated conditions in provocative situations. If one of the elements of the zhisnogo mechanism is susceptible to anomalies, then the patient will become weak, the patient will become an object for the invasion of children.

Diagnosis of primary immune deficiency

Immunodeficiency stays are identified by type, some of the primary VD are most frequent, then this type of appearance starts in the first month. Vizit to lykary obovyazkovy with frequent ailments of the baby, chills, development of fungal, virgin, bacterial infections. Anomalies in the development of a child may be due to the primary immunodeficiency. To find out the problem is necessary to diagnose the term and an uncompromising ear of love.

The method of identifying ill health includes advancing procedures:

• zalnyy look, with a kind of animal respect for the training of shkіri, mucous, gnіynichkovі processes, pіdshkіrnі fatty tissue;
• the advancement of leukocyte formulas for a blood test, about VD, to speak about the manifestation of leukopenia, neutropenia, agranulocytosis, and others;
• biochemistry of blood, showing dysgammaglobulinemia, the presence of uncharacteristic metabolites, which indicate the primary humoral VD;
• specific dosage on the reaction of the immune system. Indicators of the activity of immunocompetent cells are obtained;
• molecular genetic analysis - a method of gene sequencing for the type of mutation. Tse of ways of establishing the syndrome of Bruton, Di George, Duncan, Viskott-Oldrich.

Likar differentiation of immunodeficiency diseases from the accumulated secondary IDs, which are found in the form of radioactivity, toxic speech, autoimmune ailments, oncology. In older adults, the diagnosis can be put smoothly, there are some signs of smoothening, the symptomatology is not obvious.

Prenatal diagnosis

The designation of the primary VD for the additional biopsy of the chorionic villi is called prenatal identification of the form of illness. In addition, the culture of fruit waters and fetal blood grows. Tse folding analyzes, which are shown in quiet drops, since a mutagen has been detected in the fathers.

For the detection of an X-marked important combined immunodeficiency, we can give an accurate result, as well as clarify the diagnosis for primary VD syndromes, chronic granulomatosis, and other TKID stans.

Lіkuvannya primary immunodeficiency

Diagnosis of ethology and pathogenesis of illness does not allow virobite methodology of therapy of pathology. In case of important forms, therapeutic treatment is not relevant, it is not necessary to bring a deprivation of time lodging, a lethal result inevitably leads to an acceleration of immunodeficiency. In cich vipadkah, transplantation of the cystic marrow of an abdominal substance of the thymus root can help.

Deficiency of the immune system is compensated for by the method of storing specific colony-stimulating drugs. The price of immunotherapy is thymalin, tactically, with levamisole and other methods, which can be used by the immunologist. Fermentopathies are recognized by enzymes, metabolites. Let us expand the drug to a number of є biotin.

Disglobulin (lack of humoral disease) favor immunoglobulin substitutions, in the presence of such defective species. It’s a headache for the progression of ill health є prevention of infections. Moreover, the vaccination of ailments on the first VD of children does not give an effect, it is not safe.

Forecast and prevention

In case of important primary VD children of adjectives, win guine in the first ric of life. The Іnshi pathology of the immune system and vilikovyatsya, as described by the viscera. The main zavdannyam batkіv є the beast to the lіkar і look after the children. It is not possible to allow infestation of babies with virgin, bacterial, fungal buds.

If you are planning a child's population and if you have problems with genetic mutation, then consultation with an immunologist will help you. It is necessary to undergo prenatal diagnostics after an hour of vaginosity, beware of infections and taking into account all the recommendations of the doctor.

For the ailments of the Internal Affairs, it is important to take care of the special hygiene, peering behind the empty company, the mucous nose, the eyes are safe, they do not shy away from their integrity. Necessary balancing of food, inclusion of contacts with ailments before an hour of epidemics, medication for prevention of infectious diseases.

Decrease in immunodeficiency

Primary immunodeficiencies should be produced to the point of dreadful delay. The result of the inheritance may be the death of people. Sepsis, abscesses, pneumonia, and important infections are involved in such mills. You can autoimmune sickness, if you have an immune system because of the fact that you know the power of the clitine. Growth risk of oncological illnesses and imbalance of the intestinal tract, heart-vascular system.

visnovok

Primary immunodeficiency is not dependent on virok. It is necessary to check with an immunologist on a regular basis, in order to help preserve the goodness of life and life of the whole life.

For a quote: Reznik I.B. Immunodeficiency to become GENETIC NATURE: A NEW LOOK AT THE PROBLEM // RMZ. 1998. No. 9. P. 3

In this hour, it becomes clear that the primordial immunodeficiency is not a native country, as it was accepted. However, being unaffected by the progress in the field of diagnostic methods, more than 70% of ailments do not have immunodeficiency states. Statistical guidance has clinical criteria and a panel of primary laboratory methods for diagnostics of primary immunodeficiency disorders. Nowadays, it becomes clear that primary immunodeficiency is not such a rare condition as considered before. However, despite diagnostic advances, immunodeficiency is not diagnosed in more than 70% of patients. The paper gives clinical criteria and a panel of primary laboratory diagnostic assays for primary immunodeficiencies. І.B. Reznik Kerivnik Viddilu Clinical Immunology NDI Child Hematology of the Ministry of Health of Russia, Doctor of Medical Sciences, Professor of the Russian State Medical University.

I.B. Reznik, MD, Head, Department of Clinical Immunology, Research Institute of Pediatric Hematology, Ministry of Health of the Russian Federation; Professor, Russian State Medical University.

Entry

With a normal interruption of vaginosity in the intrauterine period, the development of the child is in sterile minds. The people secretly started colonizing microorganisms. So, the main microflora is not pathogenic, but colonization is not sickness. In the general examination of pathogenic microorganisms, with children not developing, the development of infectious ailments. Skin contact with the pathogen should be brought to an expanded immunological memory and a form of additional immunity.
Chotiri basic components of the immune system and take part in the death of the individual from the persistent attacks of viruses, bacteria, fungi and the simplest, common infections of the infection. The components include intermediate antibodies, or B-cell, immunity, T-cell immunity, phagocytosis and the complement system. The skin of the ciches of systems can be independent, but also in the process of immune response to the interaction of the components of the immune system.
Endogenous, as a rule, genetically mummate a defect in one of the components of the immune system and lead to the destruction of the system and destroy the organism, and clinically appear as one of the forms of the primary immune deficiency (PID). So, as in the normal functioning of the immune system and the immune system take on the part of many types of cells and hundreds of molecules, the basis of PID lies in the number of variants of defects. Science group VOOZ, as published on the skin 2 problems on PID problems, in the last additional reasons there were more than 70 identified defects, but to lie in the basis of PID, to that date the number became 17, and 4 p. in table. 1.
An hour will remain at the link with the appearance of molecular defects, so to lie at the base of the bagatio of immunodeficiencies, and in the context of the variability of the clinical picture and the severity of interruption of the PID, the dignity of the age th rіdkіsne stan, yak tse vvazhali to tsikh pіr. For the significant part of the PID, the frequency becomes 1/25 000 - 1/100 000, if there are such variants of innate immune defects, such as a selective IgA deficiency, among the representatives of the blue race they develop at a frequency of 1/500 - 1/700 people. The total broadening of the PID of the nevidoma, protea, according to the estimates of the Immune Deficiency Foundation - IDF (USA), this indicator 4 times outweighs the frequency of cystic fibrosis.

4.2.1. Clinical and immunological characteristics of options for pids

Spadkova hipogamaglobulinemia (Bruton's ailment)

1) the presence of membrane IgM / IgD receptors (BCR) on CD19 + lymphocytes;

2) from the appearance of the expression of cych immunoglobulins on CD19 + membranes - lymphocytes.

The first variant of dressings with a close differentiation of B-lymphocytes in the adult cells at the stage of transformation in the plasma cells. Another option can be an inherited mutation of genes, which control the synthesis of important lances (deletion of genes on 14 chromosomes).

Described is the pattern of vypadkіvі vіdnosti B-lymphocytes in the blood of females, albeit smelly stinky homozygous for the X-chromosomal mutation, as they showed clinically.

Zagalny variable immune deficiency (hypogammaglobulinemia, hypogammaglobulinemia in adults)

A common manifestation of dysimmunoglobulinemia є zagalnaya variable immune deficiency (clunny). Vona develops for the development of the deterioration of the building B-lymphocytes are transformed into plasma cells. Laboratory diagnostics primed on the detected total concentration of IgM, IgG, IgA<300 мг%. В клинике чаще всего отмечаются рецидивирующие и хроническиемикробно-воспалительныепроцесы ЛОР-органов, глаз, легких, ЖКТ, гнойные поражения кожи. У детей с ОВИН не формируется специфический поствакцинальный иммунитет. У 1/3 больных отмечается сопутствующая анемия. Характерныгиперплазия лимфоузлов, кольца Пирогова-Вальдейера, увеличениеселезенки.ОВИН предрасполагает к аутоиммунным процессам. У взрослых больных с ОВИН часто развиваетсявосходящий холангит,желчекаменнаяболезнь, артриты и атопические процессы. Заболевание может манифестировать в разном возрасте (детском, подростковом или юношеском, средний возраст пациентов - 25 лет). Как правило, количествоВ-лимфоцитов в крови не снижено,но эти клетки не способны синтезировать иммуноглобулины какого-либо класса, чаще всегоIgG. Очень часто отмечается нарушение функционального состояния В-лимфоцитов. Предполагаются следующие механизмы развития ОВИН: поражениеCD19+-клеток, недостаточность функцийCD4+, дефицит цитокинов, отсутствие кооперации между Т- и В- лимфоцитами вследствие нарушения экспресссииCD40+. Предполагается полигенная природа заболевания. В основе патогенеза могут лежать дефекты одного или нескольких геновHLAIII.

deficiency of subclasses IgG

Vidomo 4 subclass IgG. IDS develops when there is a deficiency of cutaneous podclases, or when there is a whole level of zagalny IgG in the norm. It is possible to evolve the stance only from specific antisoids to the skin subclasses. So, as the dosage of clones B-lymphocytes, secreting IgG2 and IgG4 and not before another fate of life, in children of early age є physiological deficiency of cych subclasses. IgG4 deficiency occurs in 13 - 20%, IgG2 in 50% of cases of ailments with primary IDS. Deficient IgG1 most often can be compensated clinically for the establishment of antibodies of other subclasses. The classic picture is dominated by recurrent infections of dysfunctional nobles.

selective deficiency Ig A

There is one of the most common forms of the primary IDS, which are formed in 1: 100 - 1: 700 vipadkiv. With a whole zm_st IgA in syrovatts_ blood less than 5 mg% (0.05 g / l). The Іnshі indicators of humoral immunity and functional stan- dard of clerical immunity are not impaired. See 4 options:

1) without critical manifestations;

2) in case of ataxia - teleangiectasis (Luї-Bar syndrome);

3) in response to IDS with the advancement of IgM synthesis;

4) in response to chromosomal mutations.

In the classroom, pathological processes in the ENT organs and the broncho-legacy system are most often observed. As a rule, there is a decrease in plasma and secretory levels of IgA, moreover, offending this subclass. Yak vidomo, IgA acts an alternative cascade of reactions to complement and low bactericidal activity. When the IgA is out of the way, the secretions are released for clear access to allergens and microbial antigens in the tissue and to prevent direct contact with the cells-effectors. It is clinically manifested by allergic and autoimmune reactions, dysbacteriosis and ignited discomfort in the intestinal tract. Approximately 40% of patients have antibodies to IgA, which can be classified as IgG. major defect , The development of selective IDS IgA consists of a deteriorated thermal differentiation of B lymphocytes. In addition, the role is played by those in which the violation of IgA is inherited as a monogenic sign, and the main manifestation of polymorphism. Selective deficiency IgA refers to uncorrected defects in immunity. The function of CD3 + -clitin is not damaged. Anomalies of intermixing of isotypes and defects of cytokines are transmitted, which regulate the processes.

Immunodeficiency due to increased synthesis of I gM

When the form of IDS changes, IgM changes 300 mg% (0.3 g / l) and changes from 3.0 to 10 g / l, with the whole class of immunoglobulins, as a rule, decreases (IgG<200 мг%,IgA<5 мг%).. Кроме повышенной чувствительности к инфекции у таких больных отмечается образование аутоантител к гранулоцитам, тромбоцитам, склонность к аутоиммунным заболеваниям. Наследуется по рецессивному типу. При этом синдроме отмечается низкая активностьCD4+- иCD19+- лимфоцитов у Newborns, so that the basis of the defect is a defect in changing the synthesis of immunoglobulins to the "grown-up" type (with overgrowth of IgG). Slid mothers on uvaz, but also the X-linked form of the IDS with the addition of IgM is also X-linked, which is linked to the destruction of the CD40Li synthesis to be applied before the combined IDS. At the heart of the pathogenesis of autosomal form is a defect in the cytidine desaminase gene, X-genesis is a lack of T-clitin, amalgamated with mutations in the CD40 gene.

Minusch hypogammaglobulinemia children

The whole transient immunodeficiency is carried to malik, good, but often forms of primary IDS. According to the day, it is a variant of the physiological start of the synthesis of volatile IgG after the period of natural catabolism of maternal (placental) IgG, but it is infused until the 3rd month of life, but the synthesis of which is mutilated in the norm is 1-muted. Laboratory diagnostics primed on the basis of the IgG<0,5 г/л, а такжеIgA<0,02 г/л иIgM<0,04 г/л. Характерны частые респираторные инфекции, патология ЛОР-органов, кожи, дисьактериоз ЖКТ. Транзиторная гипогаммаглобулинемия детского возраста проходит без лечения к 1,5-3 годам.

Syndrome s hyper- I g E - emiya

Described in 1966r. Devisom and spivavt. like Job's syndrome (in the nickname of a sick person). To appear in the first month of life of the disease on generalization of eczematous dermatitis. 60-70% of the sick are lads. Take care of the shkіra of revealing, shia, hairy part of the head. Types of rhinitis, conjunctivitis. Scars, adhesions, "cold" abscesses appear on the screen. It stands to reason more strongly. In blood eosinophilia, often - neutrophillosis due to hypotension. IgE structures have anti-staphylococcal antibodies in high titers (there is only one name - Staphylococcus aureus syndrome with increased IgE). A decrease in IgG, a decrease in the chemotaxis of granulocytes, is indicated, in fact, for the increase in great concentrations of histamine, which is caused by the activation of stem-boron cells. The sickness generates a great number of toxic radicals, which is responsible for the establishment of cold abscesses in pediatric cells. Job's syndrome calms down in an autosomal recessive type.

Spadkov and the genesis of T-cell pathology to immunity to manifest itself at different stages of the maturation of T-clitin - from a stovburovoy clitin to the development of specialized subpopulations.

Lymphocytic dysgenesis (Nezelof syndrome, French type PID)

For a given IDS, the type of functional deficiency is the lack of T-cell immunity to normal immunoglobulin. Described in 1964 p. Nezelof. To settle down in an autosomal recessive type and to manifest itself in the first time and life. It is evident that there is a retardation of the development, a prolonged septic process with gn_ynymi vognischi in the skin, lungs, fungal sepsis does not develop rapidly. Variations of thymus hypoplasia and lymph nodes. In the blood - a very low level of CD3 + lymphocytes, a low appearance in RBTL and HRT, a decrease in the function of CD16 + clitin. Most often the prognosis of unpleasantness.

Hypoplasia of the thymus and parathyroid vines ( c Іndra Di-Georgі)

Described by the author in 1965, they were tied with a defect in the diaphragm differentiation in the area of ​​the 3rd and 4th pharyngeal colonies. Often sickness is a woman. To be seen from the first days of life at the viglyadі by the court (for the reduction of Ca ++), the infection of the dying urine paths, the poisoning of the etching. It is not easy to go with the vads of the development of the great Sudins and the heart (extravaginal arterial blood flow, subjunction of the aortic arch, dextrocardia and іn.). The immunogram is similar to Neselof's syndrome. In the spectrum of infectious antigens, pathological processes are affected, viruses, tuberculosis bacteria, fungi and bacterium bacteria.

combined immunodeficiency

Spadkovy limfocytoftyz (Swiss type PID)

Appear in the first month of life: anorexia, bark similar to visipus, thrush, shkirny candidiasis, interstitial pneumonia, viral infections. To settle down in an autosomal recessive type of abnormal condition (75% - lads). It is characterized by a decrease in the number of CD3 + -. to a lesser extent CD19 + lymphocytes with impaired functional activity. Hypoplasia of lymphoid tissue is indicated. Some children have a thymic defect, in some cases CD3 + lymphocytes DO NOT express HLA-antigenii III - "naked lymphocyte syndrome". In the absence of HLAII (DR, DQ, DP), it is characteristic to experience the syndrome of impaired moisture (malabsorption).

PID with Tim (Hood's syndrome)

Characterized by hyperplasia of the thymus due to the growth of stroma, lymphocytopenia, low volume of immunoglobulins in the blood. Zupinka in the development of the thymus veda until the formation of IDS with Tim, which is characterized by a further lack of CD3 + - and CD19 + lymphocytes. It is transmitted, but the main defect manifests itself at the early stages of differentiation of stovburovicheskikh clitin. Talking about the opposite, there is a deficiency of erythroblasts in the cystic marrow and aplastic anemia. The pathogenetic mechanism and data about the decline of the given syndrome are still little known.

Wiskott-Oldrich syndrome

Described in 1937 for a family X-syndrome (in lads). There are three symptoms: 1) becoming sick to recurrent and chronic infections of the respiratory system and ENT organs, 2) hemorrhagic syndrome in connection with thrombocytopenia, 3) atopic dermatitis due to eczema. Appear from the period of new birth. Hypofunction of the thymus is indicated, a decrease in hemoglobin and erythrocytes, eosinophilia, a decrease in platelet defects (impaired adhesion, aggregation, decrease in ATF). Characteristics of petechiae, hemorrhage from mucous membranes. The shock of the shkiri is recurrent in nature. In the immunogram, IgM most often decreases with normal IgG, and IgA and IgE adjustments. The basis of the defect is the destruction of the structure of cell membranes of lymphocytes. The prognosis is often unpleasant: children go out of infection and dystrophy.

deficiency IgA in addition to ataxi-teleangioectasis (Luї-Bar syndrome)

The manifestation of the ataxis of those neurological problems with teleangioectasis of the sclera and individuals in the presence of immunological defects is evident. The deterioration of the function of the corns is promoted (with a little more atrophy), as well as of the infantile ganglia, the diencephalic areas of measles, the great infestation of the brain, and for the breakdown of the brain it is often developed. The nature of the broken walk, the duality of strong ruffs, hyperkinesia, syndromes of parkinsonism and vegetative-freezing disorders. Often, there are low-flow pneumonia, which end with the development of atelectasis, pneumosclerosis and bronchiectasis. Chvorі grows from physical development. Hypoplasia of the thymus, lymph nodes and spleen, lymph nodes of the intestine appear. The immunogram shows a decrease in B-lymphocytes from Fc-receptors to immunoglobulins, a low appearance in RBTL, and the absence of IgA. Sickness is characterized by an autosomal recessive type of sedation. In ailments, spontaneous chromosomes appear, overwhelm in 7 and 14 chromosomes, and damage the mechanisms of DNA repair. Forecast of unpleasantness.

lack of IL -2

Described in 1983r. With a whole day, the proliferative process on PHA and Kona with normal cell lymphocytes. It also affects the impairment of the proliferative activity of cytin for the loss of IL-2.

lack of NK (SD 16)

NK cells develop anti-swelling immunity, as well as resistance to persistence of internal pathogens. Їх activate -interferon and IL-2. Such a disadvantage occurs in Chediaka-Higashi syndrome.

Duncan's ailment

The number of X-patterns of the IDS is characterized by an increased sensitivity to the Epstein-Barr virus. Lads who have had infectious mononucleosis develop trivial fever, lymphadenopathy, lymphocytosis, liver and spleen abnormalities. Instead of immunoglobulin, there is a decrease or the prevention of dysimmunoglobulinemia. Lymphoproliferative process is most often fatal result in connection with lymphoid formation with important localization in the terminal tissues of the small intestine, as well as due to liver necrosis.

Lack of complement system (C)

The complement system will make it possible for a specific person to survive in case of immune reactions to an organism. Activation to lead to direct lysis of cellini and to stimulation of phagocytic activity. The process of activation of the enzymatic systems of the intermedium proteolysis.

The classic way of activating the system and complement will prevent the fate of the formed immune complexes, including IgM, IgG1, 2, 3, a fragment of the Hageman factor, a protein of microorganisms, CRP complexes (for example, from molecules in DNA), destruction In general, there are straightening paths for the strengthening of immune cytolysis.

lack of phagocytosis

Kostman syndrome .

Described in 1956r. Appear in early childhood with recurrent bacterial infections of the scalp and scalp, pneumonia, osteomyelitis, sepsis. It is characterized by neutropenia, monocytosis, eosinophilia and anemia. In the cystic brain, there are signs of the reception of the ripening of mylocytes. Acceptance by autosomal recessive acquaintance, as in the case of congenital neutropenia (neutropenia with eosinophilia, Chediak-Higashi syndrome, pancytopenia Fanconia).

Chediaka-Higashi syndrome.

Described in 1952r. characterized by some manifestations of partial albinism of shkiri, hair and eyes, hot stuns, pancytopenia, schilosity to infectious-fiery ailments, neuropathies. Ignition processes in mucous dichal noises and on skies, most often with golden staphylococcus or gram-positive bacteria. Apparently, hepato-splenomegaly, there are blood thinning (thrombocytopenia), a septic stun is formed. Most of the ailments do not live up to the 10th century.