Immunoglobulin defects. Tolerance and the ability to distinguish between “self” and “foreign” are vital conditions for preventing reactions directed against one’s own cells and tissues, while maintaining the diversity of antigen receptors of lymphocytes, special

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Pathogenesis of selective immunoglobulin A deficiency

Clinic of selective immunoglobulin A deficiency

Treatment of selective immunoglobulin A deficiency

There are cases when patients are given a referral for a test, the significance of which they often do not know. For example, what are class A immunoglobulins? Referral for analysis immunoglobulin IgA can be received from a doctor by both children and adults. So what can this indicator tell the doctor?

What is immunoglobulin A?

Immunoglobulin A is a clear indicator of the condition humoral immunity. This protein can be contained in the body in the serum and secretory fractions (both in the blood and in the secretions of the glands). The whey fraction provides local immunity and produced in increased quantities in response to inflammatory processes. The secretory fraction is contained in body secretions - saliva, breast milk, secretory fluid in the intestines or bronchi, in tears.

The function of immunoglobulin A is to bind to harmful microorganisms and thereby prevent cell damage. A certain amount of IgA is constantly contained in the blood and gland secretions. A decrease in immunoglobulin A means deficiency immune system. An increase in immunoglobulin A is observed either with sensitization of the immune system due to systemic diseases, or (most often) – during inflammatory processes.

After it has become clear what it is - immunoglobulin A, the next question arises - for what purpose is it tested? The usual indications for such analysis are comprehensive examination with frequent infectious diseases - for example, when children often get sick colds or intestinal infections. In this case, the child’s immunoglobulin A will either be reduced, which is an indicator of immunodeficiency, or will be normal, and then the cause must be sought in other factors, or increased, which will demonstrate the current acute inflammatory process.

In other cases, an analysis for immunoglobulin class A is carried out when immunodeficiency is suspected and when monitoring the condition of patients with diagnosed immunodeficiencies, when detecting neoplasms, when diagnosing autoimmune pathologies, and to test the effectiveness of multiple myeloma treatments.

Thus, IgA is responsible for immunity indicators and is necessary for diagnosing the causes of various recurrent diseases, as well as for monitoring the immune system in various systemic diseases.

How is blood collected for analysis?

To test for immunoglobulin A, a sample is required. venous blood. Since antibodies are a very specific structure that differs from the main biochemical elements of blood, the rules for preparing for analysis for them differ from the usual ones. For example, there is no restriction on eating within 8-12 hours. You cannot eat for 3 hours before an immunoglobulin test. You can drink non-carbonated clean water.

Half an hour before the analysis, you should not be very nervous and exposed to physical activity. Therefore, if a child donates blood, the task of parents is to ensure that within the specified time period he behaves calmly and does not worry about donating blood. Should in a calm voice explain that the procedure is carried out quickly and painlessly, distract the child for some activity.

It is not advisable to drink alcohol the day before the test. Smoking should be avoided at least 3 hours before the procedure. Due to the fact that immunoglobulin A is also produced as an immune response to bronchial irritation, smoking (including vaping) can negative affect the test results.

What other factors may distort the result?

In addition to the above, there are some other factors that can affect the result. They should be taken into account by the attending physician, who will evaluate the test result. These factors include, first of all, pregnancy, which usually results in low immunoglobulin level. In addition, extensive burns can reduce the concentration of IgA, renal failure, drugs that lower immunity and different kinds irradiation.

Among the factors that increase the content of immunoglobulin A, some should be noted medications(mainly antipsychotics, anticonvulsants, antidepressants and oral contraceptives), vaccinations given less than 6 months ago, as well as excessive physical, mental and emotional stress immediately before donating blood.

In some cases, immunoglobulin A deficiency is associated with specific feature the patient’s body – it produces antibodies to its own IgA protein. Such patients are susceptible high risk damage to autoimmune diseases and infections. In addition, there is a risk of developing an anaphylactic reaction during blood transfusion or organ transplantation.

Standards for immunoglobulin A content

Due to the fact that from birth our immune system is imperfect, in infants for some time their own IgA is not produced by the body, but comes with mother’s milk (this is one of the reasons why breast-feeding so important on early stages). Norm of immunoglobulin A in children less than a year old is 0.83 g/l.

As can be seen from the standards, an adult not only has the highest upper limit permissible norm, but also the greatest variability of indicators. They may be associated with individual characteristics body, and with the action of any irritants and vary slightly even within one day.

If immunoglobulin A is elevated

If the immunoglobulin A content is beyond the upper limit, i.e. immunoglobulin A is elevated - what does this mean? Many diseases can increase IgA levels. Among the main causes are infections that affect the skin, bronchi, lungs, intestines, genitals and urinary organs. Besides, common cause increases in immunoglobulin A are various neoplasms, including malignant ones.

High concentration IgA can show up in cystic fibrosis, liver diseases, and systemic autoimmune diseases. The lifespan of immunoglobulins of this class is approximately 6-7 days, and detection increased concentration IgA in the blood means that the inflammatory process either exists in the body at the time of analysis, or was present no earlier than a week ago. If the analysis indicators are borderline, then a repeat test is carried out a week later, eliminating possible factors that distort the results.

If immunoglobulin A is reduced

Immunoglobulin A is low if the body's immune system has malfunctioned and does not produce enough proteins to protect itself. This situation occurs with HIV, removal of the spleen,... Other diseases that can cause a decrease in IgA -, chronic diseases respiratory system, colon, kidneys. In addition, a decrease in immunoglobulin A can be explained by congenital characteristics of the body, which were already mentioned earlier in the text.

Selective immunodeficiency of immunoglobulin A occurs among the population more often than other types of immunodeficiencies. By itself, it is often asymptomatic, leaving only indirect hints in the form of often recurrent infectious diseases or allergic reactions. The disease can suddenly manifest itself in a situation of stress for the body - a change climatic conditions, diet, during pregnancy and childbirth, hormonal imbalance, severe emotional stress.

Patients who do not have enough immunoglobulin A may experience various allergic reactions or develop asthma. The most common symptoms experienced by a person with selective immunoglobulin A deficiency are anaphylactic shock upon contact with previously harmless irritants, increased sensitivity respiratory system, as well as urination disorders. Less common intestinal disorders, inflammation of the conjunctiva of the eye and diseases of the lungs and bronchi.

The exact cause of selective immunoglobulin A deficiency is unknown. Various hypotheses have been put forward, including congenital features(obtained hereditarily or as a result of a random mutation), prolonged stress, bad social conditions(in particular, malnutrition), poisoning hazardous substances and oncological diseases.

Evaluation of the results obtained

A blood test for immunoglobulin A takes on average 2-3 days from the date of the test. The test is inexpensive, around 200 rubles (prices may vary depending on the specific laboratory). For adequate and full presentation about the patient’s condition, in addition to analysis for immunoglobulin A, tests are also carried out for other immunoglobulins: E, G, M.

In addition to determining the content of immunoglobulins, for a complete picture of the state of the immune system, the patient must undergo tests for general formula blood, leukocyte, ESR, protein fractions in serum. If the attending physician has reason to suspect a specific disease, then others are prescribed at his discretion. additional tests. In other words, the analysis for IgA content itself is not very informative; it is of value only when included in a full examination.

Determination of selective immunoglobulin A (IgA) deficiency

Congenital and acquired disorders of the function of T - and B-lymphocytes are associated with their quantitative deficiency or functional failure. The causes of these deviations may be associated with genetic or metabolic disorders, as well as with exposure to various infectious agents and damaging factors on the body. Purchased immunodeficiencies may be a consequence of various non-communicable diseases(tumors) and medical effects(splenectomy, plasmapheresis, cytotoxic therapy, etc.).

Violations B-systems immunity is detected by examining the content of B-lymphocytes in the blood, total immunoglobulins and immunoglobulins of the classes IgM, IgG, IgA and IgE. The presence of isohemagglutinins and antibodies to previously administered vaccine preparations in the blood of the subjects also indirectly indicate the state of the B-cell immunity.

Clinically B cell deficits most often manifest as recurrent bacterial infections, especially often caused by staphylococci, streptococci, Haemophilus influenzae and other pathogens of so-called pyogenic infections, as well as opportunistic microbes - causative agents of opportunistic infections. B cell failure is often accompanied by the development autoimmune processes. The most common of congenital immunodeficiencies is selective IgA deficiency. According to different authors, the frequency of this type of immunodeficiency varies between 1: 400-1: 800. The cause of this disease is unknown. With selective IgA deficiency in the blood, patients have B lymphocytes carrying mlgM, but the B cells have an impaired ability to differentiate into IgA-secreting plasma cells. Clinically, IgA deficiency may long time do not manifest themselves in any way, however, among people with such a deficiency, allergic ( bronchial asthma) And autoimmune diseases(systemic lupus erythematosus, rheumatoid arthritis etc.), as well as thymomas and tumors of the esophagus and lungs. Deficiency is often detected during the examination of patients suffering from infections of the sinuses and lungs. For persons with IgA deficiency, the danger is possible development post-transfusion immunopathological reactions, including intravenous administration immunoglobulins containing Ig A. These reactions are due to the accumulation of IgG antibodies against IgA immunoglobulins in such patients. Instead of secreted IgA, slgM is detected in the secretions of patients with IgA deficiency.

Among the famous immunodeficiency states Selective deficiency of immunoglobulin A (IgA) is most common in the population. In Europe, its frequency is 1/400-1/600 people, in Asia and Africa, the frequency of occurrence is somewhat lower. Selective deficiency is considered to be a state in which the level of serum IgA is less than 0.05 g/l with normal quantitative indicators of other parts of the immune system.

Selective deficit IgA. IN to a certain extent It is surprising that when screening normal sera with a certain frequency (0.03-0.97%), IgA deficiency can be detected (<50 мг/л) у клинически здоровых лиц. Очевидно, этот дефект может быть компенсирован при иммунном ответе как за счет локального синтеза Ig другого класса, так и посредством транссудации секреторного IgA через слизистые оболочки. Детальные исследования показали отсутствие IgG2 и увеличение мономерного IgM. Частота инфекционных осложнений составляет примерно 15%. У части больных обнаруживают энтеропатию. Сторонники одной теории предполагают ассоциацию данного дефекта с нарушением защитных свойств слизистой оболочки, согласно другой - определенную роль играет процесс беспрепятственного всасывания ряда антигенов, к примеру лекарственных препаратов, что приводит к интрамуральным реакциям иммунных комплексов, в частности при толерантности к глутенину. При биопсии слизистой оболочки кишечника на фоне нормальных морфологических данных было обнаружено значительное количество IgM-продуцирующих плазматических клеток при ограниченном числе плазматических клеток, секретирующих IgA. Были описаны сопутствующие заболевания, такие как ревматоидный артрит, системная красная волчанка и гемосидероз легких, однако без указания на возможные причины этих нарушений. При анализе 150 клинических случаев селективного дефицита IgA было установлено, что в 18% случаев встречался ревматоидный артрит, в 7 - СКВ, в 6 - тиреоидит, в 4 - пернициозная анемия, в 3 - хронически прогрессирующая форма гепатита. Половине обследованных больных был поставлен диагноз аутоиммунного заболевания. Довольно часто выявляют преципитирующие антитела к белкам, содержащимся в сыворотке и молоке жвачных животных. С помощью специфической козьей сыворотки к IgA человека можно распознать замаскированный IgA или убедиться в его отсутствии. Примерно у 40% больных были обнаружены циркулирующие антитела анти-IgA, что можно объяснить анафилактической реакцией больного на переливание крови или плазмы. По этой причине необходимо использовать для гемотрансфузии многократно отмытые эритроциты. Большинство авторов отводят анти-IgA значительную роль в патогенезе (угнетение продукции IgA). Приблизительно в 35% случаев выявляют анти-IgG, в отдельных случаях - анти-IgM. Содержание mIgA-несущих клеток в периферической крови в целом незначительно отличается от нормы; очевидно, нарушается процесс преобразования В-клетки в IgA-продуцирующую клетку, что может ассоциировать с активацией "классоспецифичных" клеток-супрессоров. Поскольку В-клетки обнаруживаются в периферической крови больных с дефицитом IgA, то можно предположить, что признаком нарушения зрелых В-клеток служит одновременное присутствие на них а-цепей, что несовместимо с нормальной характеристикой зрелой В-клетки. Известны данные о присутствии в цитоплазме а-цепей. В некоторых случаях с помощью стимуляции лимфоидных клеток митогеном лаконоса in vitro удается вызвать продукцию и секрецию IgA. Данные о наследовании дефицита IgA противоречивы. В большинстве сообщений отсутствуют указания на возможность генетически обусловленного дефекта, частота его в семьях свидетельствует как об аутосомно-доминантном, так и рецессивном типах наследования. Наиболее часто обнаруживают аномалии хромосомы 18, в частности делецию ее длинного плеча и другие нарушения. Частота соответствия дефекта у детей и родителей свидетельствует о возможной патогенетической роли трансплацентарного переноса антител класса IgA. Дефицит секреторного IgA может быть обусловлен нарушением синтеза секреторного компонента, к тому же получены данные о нарушении процесса миграции IgA-секретирующих В-клеток в слизистой оболочке. В этих случаях концентрация сывороточного IgA поддерживается на нормальном уровне.

Selective deficit immunoglobulins at immunodeficiency Along with hypogammaglobulinemia, which can manifest as immunodeficiency of the three main classes of Ig, conditions associated with a selective deficiency of one of the Ig classes or with a combined deficiency have been described. As observations have shown, variable Ig deficiency can be detected in 0.5% of patients examined in the clinic. Very often this condition is referred to as dysgammaglobulinemia However, the term is also used to describe other forms of Ig deficiency.

In accordance with the existing concept of normal ontogenesis, the following situations are possible:

• a) the complete absence of typical B-cells, or the loss or "masking" of the B-cell marker (about 25% of all cases);
• b) B-cells are present, but do not turn into Ig-producing cells of a clear deficiency of T-cells (polyclonal activators are ineffective - endogenous defect);
• c) B cells can even produce Ig, but not secrete them (glycosylation defect). The cells lack the EBV receptor;
• d) impaired differentiation of B cells in vivo; Polyclonal activators are effective in vitro. In some cases, circulating inhibitors are found;
• e) ID of the humoral link, mediated by impaired activity of T-suppressors (about 20%). Transitional forms to the violations indicated in paragraph "d".

It has been shown in an experimental model that massive suppressor activity can lead to B cell deficiency as a secondary effect. In all likelihood, we are talking about hypogammaglobulinemia as a secondary phenomenon. An attempt was made to use high doses of prednisolone (over 100 mg per day) to treat patients with hypogammaglobulinemia with high suppressor cell activity. In some cases, a clinical effect was obtained. T cell suppressor activity can occur at different stages of B cell maturation (differentiation of pre-B cell through the Fc phase into mlg-positive B cell, differentiation of B cell into plasma cell) and, possibly, upon exposure to a plasma cell.

Experimental research and clinical observations during selective shortage IgA suggest that suppressor cells may differ in their ability to induce a deficiency of a certain class of Ig (specific T-suppressors). Improving our knowledge will make it possible in the future to develop a pathogenetic classification of these conditions.

Selective IgG deficiency is relatively rare. It manifests itself in the form of a deficiency of one or more IgG subclasses. The currently known defects correspond to certain genetic disorders, in particular, they may be the result of gene rearrangement. In this case, the genes that control the synthesis of Ig subclasses are localized on chromosome 14. Most often, IgG2 + IgG4 deficiency is determined (partly in combination with IgA). Deficiency in the form of IgGi,2,4 + IgA1 has also been described. With selective IgG4 deficiencies, recurrent upper respiratory tract infections are noted, however, as with selective IgG3, IgG1 and IgG2 deficiencies, clinical symptoms may not appear. IgG2 deficiency was observed in patients in combination with ataxia-telangiectasia and sickle cell anemia. These defects are usually missed during diagnosis, since the concentration of total IgG is normal.

Primary IgG deficiencies are not uncommon, due to an insufficient degree of heterogeneity of IgG molecules (dysgammaglobulinemia).

IgG deficiency with simultaneously high levels of IgM. In some patients with IgG deficiency, a significant increase in IgM levels is detected, in some cases up to 10 g/l. In this case, the IgA concentration can be reduced or correspond to the norm. In all patients, resistance to infectious diseases decreases, in particular, this manifests itself in the form of recurrent bronchitis and pneumonia. The defect can be either congenital (sex-linked immunodeficiency with hyper-IgM) or acquired. This condition has been described predominantly in boys. Family anamnesis showed that a decrease in Ig production may be an inherited trait. Moreover, in some cases deficit IgG may be the result of infection of the fetus by the rubella virus.

Histological study shows a rather heterogeneous picture. Along with normal morphological data, a decrease in the number of plasma cells and a number of other disorders were found in some patients. Plasma cells were PAS-positive, which is explained by the high content of the carbohydrate component against the background of a significant amount of IgM molecules. Germinal centers are detected in some cases, but may be absent, especially in congenital forms. In some patients, plasma cell infiltration of the intestinal wall, gallbladder, liver and other organs was noted. Sometimes hyperplasia of lymphoid elements is the most pronounced symptom. More often than with other humoral forms of ID, autoimmune disorders occur. Analyzing the data obtained, some authors point to a defect in the central organs, others to a partial disruption of the synthesis of Ig molecules. When discussing the issue of combining IgG deficiency with high levels of IgM, most researchers believe that in this case the feedback mechanism between the synthesis of IgM and IgG is disrupted. Globulin replacement therapy in some cases led to normalization of IgM levels. An experimental model of this condition was reproduced in chickens bursectomized after hatching. Such chickens often developed IgG deficiency with excess production of IgM. The combination of IgG and IgA deficiency with high levels of IgM has been described as an inherited, recessive syndrome. Often, a defect in Ig synthesis is accompanied by hemolytic or aplastic anemia, thrombopenia and leukopenia. Indication of a hematopoietic stem cell defect. Lymph nodes demonstrate disruption of the structure of the B-cell, thymus-independent zone. EBV-stimulated cell lines express only mlgM and mlgD. In some cases, IgM monomer is secreted. Some patients had a limited defect in the T-dependent zone.

Selective IgA deficiency. To a certain extent, it is surprising that when screening normal sera with a certain frequency (0.03-0.97%), IgA deficiency can be detected (<50 мг/л) у клинически здоровых лиц. Очевидно, этот дефект может быть компенсирован при иммунном ответе как за счет локального синтеза Ig другого класса, так и посредством транссудации секреторного IgA через слизистые оболочки. Детальные исследования показали отсутствие IgG2 и увеличение мономерного IgM. Частота инфекционных осложнений составляет примерно 15%. У части больных обнаруживают энтеропатию. Сторонники одной теории предполагают ассоциацию данного дефекта с нарушением защитных свойств слизистой оболочки, согласно другой - определенную роль играет процесс беспрепятственного всасывания ряда антигенов, к примеру лекарственных препаратов, что приводит к интрамуральным реакциям иммунных комплексов, в частности при толерантности к глутенину. При биопсии слизистой оболочки кишечника на фоне нормальных морфологических данных было обнаружено значительное количество IgM-продуцирующих плазматических клеток при ограниченном числе плазматических клеток, секретирующих IgA. Были описаны сопутствующие заболевания, такие как ревматоидный артрит, системная красная волчанка и гемосидероз легких, однако без указания на возможные причины этих нарушений. При анализе 150 клинических случаев селективного дефицита IgA было установлено, что в 18% случаев встречался ревматоидный артрит, в 7 - СКВ, в 6 - тиреоидит, в 4 - пернициозная анемия, в 3 - хронически прогрессирующая форма гепатита. Половине обследованных больных был поставлен диагноз аутоиммунного заболевания. Довольно часто выявляют преципитирующие антитела к белкам, содержащимся в сыворотке и молоке жвачных животных. С помощью специфической козьей сыворотки к IgA человека можно распознать замаскированный IgA или убедиться в его отсутствии. Примерно у 40% больных были обнаружены циркулирующие антитела анти-IgA, что можно объяснить анафилактической реакцией больного на переливание крови или плазмы. По этой причине необходимо использовать для гемотрансфузии многократно отмытые эритроциты. Большинство авторов отводят анти-IgA значительную роль в патогенезе (угнетение продукции IgA). Приблизительно в 35% случаев выявляют анти-IgG, в отдельных случаях - анти-IgM. Содержание mIgA-несущих клеток в периферической крови в целом незначительно отличается от нормы; очевидно, нарушается процесс преобразования В-клетки в IgA-продуцирующую клетку, что может ассоциировать с активацией "классоспецифичных" клеток-супрессоров. Поскольку В-клетки обнаруживаются в периферической крови больных с дефицитом IgA, то можно предположить, что признаком нарушения зрелых В-клеток служит одновременное присутствие на них а-цепей, что несовместимо с нормальной характеристикой зрелой В-клетки. Известны данные о присутствии в цитоплазме а-цепей. В некоторых случаях с помощью стимуляции лимфоидных клеток митогеном лаконоса in vitro удается вызвать продукцию и секрецию IgA.

Data on the inheritance of IgA deficiency are contradictory. Most reports do not indicate the possibility of a genetically determined defect; its frequency in families indicates both autosomal dominant and recessive types of inheritance. The most frequently detected abnormalities are chromosome 18, in particular deletion of its long arm and other disorders. The frequency of correspondence of the defect in children and parents indicates a possible pathogenetic role of transplacental transfer of IgA class antibodies.

Deficiency of secretory IgA may be due to a violation of the synthesis of the secretory component; in addition, data have been obtained on the disruption of the process of migration of IgA-secreting B cells in the mucous membrane. In these cases, the concentration of serum IgA is maintained at normal levels.

Complete or almost complete (< 10 мг%) отсутствие IgA in serum and its secretion by B lymphocytes is the most common violation of humoral immunity. The frequency of this immunodeficiency, even among practically healthy donors, is, according to some data, 0.33%.

Genetics and pathogenesis immunoglobulin A deficiency(IgA). The molecular basis of the deficiency remains unknown. As with OVGG, the number and phenotype of blood B lymphocytes are normal. Sometimes IgA deficiency resolves spontaneously or after discontinuation of phenytoin. Analysis of pedigrees indicates autosomal dominant inheritance of this syndrome and different expressivity of the same gene.

Isolated IgA deficiency often observed in families of patients with OVGG. Moreover, this syndrome can progress to OVHGG, and the discovery of rare alleles and deletions of HLA class III genes in both conditions indicates that the defective gene common to them is localized precisely in this region of chromosome 6. IgA deficiency was observed in patients receiving the same drugs that provoke the development of OVGG (phenytoin, penicillamine, gold and sulfasalazine), which indicates the role of external factors in the pathogenesis of this syndrome.

Clinical manifestations immunoglobulin A deficiency(IgA). Infections primarily affect the respiratory, digestive and genitourinary systems. The causative agents are the same bacteria as in other disorders of humoral immunity. With intranasal administration of inactivated polio vaccine, local production of antibodies of the IgM and IgG classes is observed. The concentration of immunoglobulins in the serum, except IgA, is usually normal, although cases of deficiency of IgG2 (and other IgG subclasses) and the presence of monomeric IgM, the total level of which is usually elevated, have been described.

Patients often find antibodies to cow's milk and whey proteins of ruminants. Therefore, determination of IgA using goat (but not rabbit) antiserum may give false-positive results. Adult patients with this syndrome sometimes have celiac disease, which does not always disappear when gluten is eliminated from the diet. Autoantibodies and autoimmune diseases are often found; The prevalence of malignant tumors has also increased.

Almost 44% of patients have antibodies to IgA. If they belong to the IgE class, severe and even fatal anaphylactic reactions can occur after intravenous administration of blood products containing IgA. Therefore, such preparations must be washed 5 times (in a volume of 200 ml). Intravenous administration of immunoglobulin (more than 99% consisting of IgG) is not indicated, since in most patients the production of IgG antibodies is preserved. In addition, many intravenous immunoglobulin preparations contain IgA and can cause anaphylactic reactions.

1. General events

A. Avoid administration of live antiviral vaccines, especially if cell-mediated immune deficiency or X-linked agammaglobulinemia is suspected.

b. Blood transfusion in the absence of cellular immunity can cause a fatal complication - graft-versus-host disease. To avoid this, frozen and washed red blood cells, platelets and plasma are irradiated (50 Gy).

2. Insufficiency of humoral immunity

A.Diagnostics

1) X-linked agammaglobulinemia. The disease manifests itself in boys approximately between 6 and 12 months of life with repeated bacterial pneumonia. Patients have sharply reduced levels of IgG (less than 150 mg%), IgM and IgA. There are no B lymphocytes in the peripheral blood, which is caused by a defect or absence of the tyrosine kinase necessary for their maturation. The diagnosis of X-linked agammaglobulinemia can be established at birth by the absence of B lymphocytes in the umbilical cord blood. Neutropenia, thrombocytopenia and hemolytic anemia are possible. Patients are especially susceptible to enterovirus infections (poliomyelitis). The administration of live antiviral vaccines is contraindicated.

2) The term “unclassified immunodeficiency” refers to the lack of production of specific antibodies that is not due to X-linked agammaglobulinemia. B lymphocytes are not capable of synthesizing and secreting normal immunoglobulins. The disease affects both boys and girls.

3) With IgA deficiency, the level of IgA in the blood is less than 5 mg%. IgG, IgM levels and antibody production are normal. Secretory IgA is the main immunoglobulin in the secretions of the upper respiratory tract and gastrointestinal tract, as well as in breast milk. Deficiency of the secretory form of IgA can be accompanied by sinusitis, pneumonia, diarrhea and malabsorption syndrome, although in most cases there are no clinical manifestations. If symptoms are present, IgG 2 deficiency, which may be associated with IgA deficiency, should be ruled out.

4) Transient hypogammaglobulinemia in infants. Sometimes the onset of immunoglobulin synthesis in a child is delayed. In this case, the decline in IgG levels (up to 300 mg%), which is usually observed at the age of 3-4 months, continues. The level of IgG remains low (often below 200 mg%), and the concentrations of IgM and IgA are within the normal range or reduced. Such children, due to antibody deficiency, are susceptible to repeated bacterial pneumonia in the period between the disappearance of maternal IgG (at the age of 6 months) and the onset of its synthesis (18–24 months). With transient hypogammaglobulinemia, infections are milder than in patients who are not capable of developing specific antibodies throughout life. The level of specific antibodies during immunization with tetanus toxoid and other protein antigens is usually normal. Clinical manifestations of transient hypogammaglobulinemia are bronchospasm, pneumonia and diarrhea.

5) Deficiency of individual IgG subclasses. There are 4 subclasses of IgG. There may be a marked decrease in serum IgG 2 and IgG 3 levels against the background of a normal level of total IgG. As with the complete absence of IgG, patients are susceptible to recurrent infections. Antibodies to polysaccharide antigens (components of the cell wall of pneumococci, Haemophilus influenzae type B) are often not produced. In isolated IgG 2 deficiency, the immune response to protein antigens, as well as to the conjugate vaccine against Haemophilus influenzae, is normal. In healthy children under 2 years of age, the level of IgG 2 is reduced, so determining individual IgG subclasses is advisable only at a later age.

b.Treatment

1) Prophylactic antibiotic therapy reduces the incidence of recurrent bacterial infections. Antibiotics are prescribed for a long time or only during periods of increased risk of infectious diseases. Side effects - allergic reactions, diarrhea, pseudomembranous colitis, drug resistance.

2) In case of infection, urgent antimicrobial therapy is indicated. For bronchiectasis, massage, postural drainage and antibiotics are prescribed; for malabsorption syndrome and diarrhea, a diet is necessary.

3) Children with recurrent otitis media need hearing testing to prevent speech impairment.

4) Immunoglobulin replacement therapy- a highly effective means of combating frequent infections with insufficient humoral immunity. Patients with X-linked agammaglobulinemia and unclassified immunodeficiency require lifelong IV immunoglobulin. Less commonly, intravenous immunoglobulin is used for other forms of antibody deficiency.

A)Immunoglobulin for intravenous administration prescribed when it is necessary to administer large doses of IgG (400-500 mg/kg every 3-4 weeks). The plasma IgG level should be greater than 600 mg%. Sometimes increasing the dose and more frequent use of the drug is indicated to prevent infections. If side effects occur (fever, chills, nausea), the frequency of administration is reduced, and then paracetamol or aspirin and diphenhydramine are pre-prescribed.

b) With IgA deficiency, anaphylactic reactions to immunoglobulin are possible. In such cases, a drug that does not contain IgA (Gammagard) is safer.

V)Immunoglobulin for intramuscular administration. The saturating dose is 1.8 ml/kg, then 0.6 ml/kg (100 mg/kg) every 3-4 weeks. Rarely used because IV administration provides a higher concentration of IgG and is less painful.

5) The patient's relatives are examined to identify immunodeficiency.

3. Insufficiency of cellular immunity

A.Pathophysiology. Peripheral T lymphocytes are formed as a result of differentiation and maturation of lymphoid stem cells under the influence of the thymus. T lymphocytes are responsible for protection against viral and fungal infections and regulate the synthesis of immunoglobulins.

b.Diagnostics

1) DiGeorge syndrome(congenital aplasia of the thymus) occurs due to a defect in the development of the third and fourth pharyngeal pouches, which leads to the absence of the thymus and parathyroid glands, heart defects and a characteristic facial type. The disease can be suspected on the basis of neonatal tetany, heart murmurs and the absence of a thymic shadow on the radiograph. The number of T-lymphocytes is reduced, their proliferative reaction is weakened.

2) Candidiasis of the skin and mucous membranes. Candida albicans causes recurrent lesions of the fingernails, toenails, mouth and vagina. In such patients, there are disorders of humoral immunity and autoimmune disorders with damage to the adrenal glands and thyroid gland, which leads to primary adrenal insufficiency and hypothyroidism.

3) Other violations. Exhaustion, immunosuppressants, and lymphopenia also lead to impaired cellular immunity.

V.Treatment

1) DiGeorge syndrome. Thymic aplasia is in most cases not complete, and T-lymphocyte function is gradually restored without treatment. Fetal thymus transplantation is effective but rarely used. Until cellular immunity is normalized, it is necessary to irradiate blood products for transfusion and avoid the administration of live antiviral vaccines.

2) Candidiasis of the skin and mucous membranes. The drug of choice is prophylactic oral administration of ketoconazole.

3) Associated endocrine disorders require treatment.

4. Combined deficiency of cellular and humoral immunity

A.Diagnostics

1) Severe combined immunodeficiency- hereditary X-linked or autosomal recessive disease. In the latter case, adenosine deaminase or nucleoside phosphorylase is absent. In patients, the differentiation of lymphoid stem cells is impaired, and therefore, cellular and humoral immunity is incomplete. Often, in the first 2-3 months of life, the disease does not manifest itself clinically, and then a characteristic triad develops - candidiasis, diarrhea and pneumonitis. Boys get sick 3 times more often than girls.

A)Diagnosis diagnosed on the basis of low levels of immunoglobulins, lack of production of specific antibodies, a decrease in the number of T-lymphocytes in peripheral and umbilical cord blood and a violation of their proliferative reaction. The activity of erythrocyte adenosine deaminase is assessed. If immunodeficiency is accompanied by adenosine deaminase deficiency, prenatal diagnosis is possible by the absence of enzyme activity in fibroblast culture from amniotic fluid.

b) With adenosine deaminase deficiency, bone changes are visible on x-rays of the chest, pelvis and spine.

V) In case of maternal-fetal transfusion or accidental transfusion of non-irradiated blood to a child, the disease is complicated by graft-versus-host reaction, manifested by rash, diarrhea, hepatosplenomegaly, and delayed physical development.

2) Wiskott-Aldrich syndrome- hereditary X-linked disease. It is characterized by eczema. A decrease in the number of T-lymphocytes, a decrease in their proliferative reaction and the absence of the production of antibodies to carbohydrate antigens are detected. Thrombocytopenia, reduction in size and functional inferiority of platelets are also noted. The main causes of death are bleeding and recurrent viral, fungal and bacterial infections.

3) Diagnostic signs of ataxia-telangiectasia- ataxia, choreoathetosis, dysarthria, telangiectasia, sinusitis, pneumonia. IgA deficiency and T-lymphocyte dysfunction are often detected. Alpha-fetoprotein levels are often elevated.

4) IgE hyperproduction syndrome characterized by recurrent purulent infections, primarily skin abscesses caused by Staphylococcus aureus. Serum IgE levels are high. Antistaphylococcal antibodies of the IgE class are detected in some children. The interaction of these antibodies with staphylococci disrupts the opsonization of the latter IgG, which makes it impossible for the bacteria to be captured and destroyed by phagocytes. Laboratory studies also often reveal low production of specific antibodies and a weakened proliferative response of T lymphocytes in response to antigen.

5) Omen syndrome- a type of severe combined immunodeficiency - manifested by recurrent severe bacterial and fungal infections, diffuse erythroderma, chronic diarrhea, hepatosplenomegaly and delayed physical development. Blood tests reveal eosinophilia; the total number of lymphocytes is normal, but the number of clones decreases.

b.Treatment

1) In severe immunodeficiencies (severe combined immunodeficiency, Ohman and Wiskott-Aldrich syndromes), bone marrow transplantation is necessary. The donor must be HLA compatible. To ensure engraftment, partially preserved immune system function is suppressed before transplantation. Complications of bone marrow transplantation include graft-versus-host disease and infections.

2) For Wiskott-Aldrich syndrome splenectomy is performed. To prevent bacterial sepsis, TMP/SMC or ampicillin is prescribed before surgery. Treat eczema. The only radical treatment is bone marrow transplantation.

3) Active antimicrobial therapy is necessary. The causative agents of infections can be various microorganisms. For Pneumocystis pneumonia, TMP/SMC and pentamidine are used.

4) Due to the lack of humoral immunity, all patients are prescribed intravenous immunoglobulin.

5) Siblings of children with severe combined immunodeficiency should be isolated from birth and tested for this pathology.

5. Phagocytosis disorders and complement component deficiency

A.Neutrophil dysfunction.

b.Complement component deficiency

1) C1 deficiency is observed in lupus syndrome and is manifested by frequent bacterial infections.

2) C2 deficiency is observed in hemorrhagic vasculitis and SLE.

3) Deficiency of C3 and C3b inhibitor results in frequent purulent infections. Deficiency may be congenital. It is also seen in nephritis and C3-wasting diseases (SLE).

4) C4 deficiency is observed in SLE.

5) C5 deficiency is observed in SLE and is associated with frequent infections caused by Neisseria spp.

6) C7 deficiency is observed in Raynaud's syndrome and is manifested by infections caused by Neisseria spp.

7) Deficiency of C7 and C8 results in frequent infections caused by Neisseria spp.

8) Recurrent infections are treated with antibiotics.

V.Dysfunction of the spleen. The spleen plays an important role in the phagocytic system. When its function decreases, severe bacterial infections often occur, primarily pneumonia.

1) Pathophysiology

A) Asplenia (congenital absence of the spleen, previous splenectomy) or functional asplenism (hypofunction of the spleen, for example in sickle cell anemia).

b) In patients who underwent splenectomy before the age of 2 years, the processing of polysaccharide antigens (antigens of the capsule of pneumococci or Haemophilus influenzae) is impaired.

2) Treatment

A) For infection, antibiotic therapy is indicated. In the case of asplenia or functional asplenism, the risk of sepsis is increased, so intravenous antibiotics are started without waiting for culture results.

b)Prevention of infections

i) Phenoxymethylpenicillin, 125 mg orally 2 times a day, or ampicillin, 250 mg orally 2 times a day, is prescribed prophylactically.

ii) It is necessary to warn parents that any infection in a child is dangerous and that at the first sign of it, they should immediately consult a doctor. If immediate medical attention is not possible, parents are provided with oral antibiotics, which should be given to the child if symptoms of infection appear.

iii) Early immunization with all bacterial subunit and conjugate vaccines is indicated.

6. Hereditary angioedema is an autosomal dominant disorder in which dysfunction or deficiency of the C1 inhibitor leads to uncontrolled activation of C1, consumption of C4 and C2, and release of a vasoactive peptide that causes edema. After the slightest injury or emotional stress, or even without any apparent reason, transient swelling of the face and limbs appears, not accompanied by itching. Swelling of the mucous membrane of the upper respiratory tract is possible, which leads to obstruction of the larynx and asphyxia. Abdominal pain, vomiting and diarrhea arising from swelling of the intestinal wall can be observed without skin manifestations. Urticaria is not typical for this disease.

A.Diagnostics. In most cases, the level of C1-esterase inhibitor is reduced, but in approximately 15% of patients the level of the inactive enzyme is normal. Both options are characterized by low level C4, which decreases even more during exacerbation.

b.Treatment

1) The most dangerous complication of an attack is swelling of the larynx, so sick children and their parents are informed of the need to immediately seek medical help if they experience hoarseness, changes in voice, or difficulty breathing or swallowing. For laryngeal obstruction, tracheotomy is necessary. In hereditary angioedema, unlike anaphylactic shock, adrenaline and hydrocortisone are usually ineffective.

2) During attacks, a purified C1-esterase inhibitor is effective.

3) Androgens have been shown to stimulate the synthesis of C1-esterase. Regular intake of danazol (50-600 mg/day) or stanozolol (2 mg/day) significantly reduces the frequency and severity of attacks.

J. Gref (ed.) "Pediatrics", Moscow, "Practice", 1997