home Audience 3 Selective immunoglobulin A deficiency: symptoms, diagnosis, treatment. Selective IgA deficiency

Selective immunoglobulin A deficiency: symptoms, diagnosis, treatment. Selective IgA deficiency

Selective IgA deficiency is the most common primary immunodeficiency condition (PIDS). The incidence of patients with selective IgA deficiency ranges from 1:400 to 1:1000 in the Caucasian population and is significantly lower, from 1:4000 to 1:20000, in the Mongoloid population. In the United States, the prevalence of the disease ranges from 1 in 223-1000 in the study group to 1 in 400-3000 in healthy blood donors. Similar studies have not been conducted in Russia.

This condition is characterized by a selective decrease in serum IgA concentration below 0.05 g/L (in children over four years of age) with normal levels of other serum immunoglobulins, a normal serum antibody response and a normal cell-mediated immune response. In most studies, the frequency of occurrence among males and females was approximately the same.

People with an inability to produce IgA may remain asymptomatic due to compensation mechanisms or suffer from frequent respiratory, digestive or genitourinary system, gastroenterological pathology (for example, celiac disease), a tendency to atopic disorders such as hay fever, bronchial asthma, atopic dermatitis, IgE-mediated food allergy, as well as neurological and autoimmune diseases (most often rheumatoid arthritis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, Sjogren's syndrome). For selective IgA deficiency allergic diseases, such as atopic dermatitis and bronchial asthma, occurred in 40% of cases (Consilium Medicum, 2006). Also typical for most of these patients are anaphylactic reactions during transfusion of blood components and the administration of intravenous immunoglobulins, which is associated with the presence of IgA in these products.

Clinical symptoms of selective IgA deficiency can manifest in early childhood, with age, the frequency and severity of transmitted infections can decrease due to a compensatory increase in antibodies of the IgG1 and G3, IgM subclasses. Another explanation for the absence of clinical symptoms may be the normal level of secretory IgA, despite a decrease in serum immunoglobulin levels. Or, on the contrary, some patients with initially diagnosed selective IgA deficiency may develop a clinical picture of common variable immune deficiency.

Therapy for selective IgA deficiency currently consists of identifying concomitant diseases, preventive measures measures to reduce the risk of infection, as well as quickly and effectively treat infections.

There is no specific treatment. The prognosis for patients with IgA deficiency is generally good if there are no significant clinical manifestations. IgA deficiency in children can be corrected over time.

Being genetically determined, immunodeficiency states arise due to defects in the genetic apparatus. Patients with common variable immune deficiency and those with selective IgA deficiency are often found in the same family and have a common HLA haplotype; many have rare alleles and gene deletions within the MSI class 3 on chromosome 6. Recently, some familial cases of common variable immune deficiency and selective IgA deficiency have been shown to be caused by a mutation in the TNFRSF13B gene, which encodes a protein known as TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interactor). It is likely that in cases where no TACI mutation was found, the cause of the disease could be spontaneous or hereditary mutations other genes that have not yet been recorded.

Currently, possible clinical manifestations of selective IgA deficiency, course variants, and possible concomitant diseases have been described in sufficient detail. Decisive in the diagnosis of the disease is a selective decrease in the serum concentration of IgA in children starting from 4 years of age below 0.05 g/l with normal levels of other serum immunoglobulins in repeated immunograms. Treatment consists of identifying concomitant diseases, taking preventive measures to reduce the risk of infection, and also requires prompt and effective treatment infectious diseases.

There is no information on the frequency of occurrence of this primary immunodeficiency condition in the Russian population, which does not make it possible to compare the prevalence of the disease in our country with other countries where similar studies have already been conducted.

The main problem is the lack of uniform recommendations for the management of patients with selective IgA deficiency.

In order to assess the frequency of occurrence of selective IgA deficiency among children in the “frequently ill children” group of dispensary observation and to characterize the range of its clinical manifestations in Russian Federation on the basis of the Federal State Budgetary Institution "FNKTs DGOI named after Dmitry Rogachev" of the Ministry of Health of the Russian Federation and the State Budgetary Institution of Children's City Clinical Hospital No. 9 named after. This work was carried out by G.N. Speransky Department of Health.

Materials and research methods

The object of the study was children with selective IgA deficiency, observed in the Children's City Clinical Hospital No. 9 named after. G. N. Speransky DZM. In addition, a retrospective analysis was carried out medical documentation for the period from 2003 to 2010. 9154 patients from the dispensary observation group “frequently ill children” (Table 1-3).

The following methods were used during the examination:

clinical and anamnestic;
general and biochemical tests blood;
immunological study of blood composition using nephelometry and flow cytometry methods;
scarification tests;
determination of specific IgE by immunoblotting;
study of external respiration function;
rhinocytological study.

The diagnosis of selective IgA deficiency was made on the basis of a selective decrease in the serum concentration of IgA below 0.05 g/l with normal levels of other serum immunoglobulins in repeated immunograms and the exclusion of others possible reasons their deficiency in children over 4 years of age.

When collecting anamnesis, special attention was paid to the frequency and range of clinical manifestations, concomitant pathology, and family history was also studied in detail. Clinical examination of children was carried out in accordance with generally accepted methods. The content of immunoglobulins of classes A, G, M, E in serum was determined by nephelometry on a BN 100 nephelometer (Dade Bering, Germany) using a Dade Behring kit. Phenotyping of lymphocytes was carried out by flow cytometry on a FacsScan device (Becton Dickenson, USA) using fluorescently labeled monoclonal antibodies Simultest (Becton Dickenson, USA). Patients with any manifestations of atopy, as well as all patients with elevated IgE levels, which were identified as a result of assessing immune status using the nephelometry method, underwent an allergological additional examination using the method of scarification tests in children over 4 years of age or by determining specific IgE in the blood serum of patients under 4 years of age. Children with a diagnosis of bronchial asthma or a history of broncho-obstructive syndrome underwent a study of external respiratory function using the Spirovit SP-1 device (Schiller AG, Switzerland). All necessary additional examinations and consultations with related specialists were also carried out, taking into account existing complaints.

Results and its discussion

A retrospective analysis of the medical records of patients with referral diagnoses of “recurrent ARVI”, “CHD”, “CHD”, as well as “EDD” made it possible to establish that the frequency of selective IgA deficiency in this group of children is two or even three times higher than in the population.

The absolute number, as well as the percentage of children with this primary immunodeficiency by year, can be seen in Table. 4.

Unfortunately, data for 2007 is not available. In 2003 and 2004 692 and 998 children were consulted. Among them, a total of 5 patients with selective IgA deficiency were identified, which is slightly more common than the population average - 1:346 and 1:333, respectively, versus 1:400-600. Since 2005, the frequency of newly diagnosed patients with this PID has increased sharply: 1:113 in 2005, 1:167 in 2006, 1:124 in 2008, 1:119 in 2009, and finally , 1:131 in 2010. During the study, the frequency of occurrence changed from 1:346 in 2003 to 1:131 in 2010, when it was the highest in comparison with previous years. The increase in the incidence of patients with selective IgA deficiency in the third year after the start of work should be associated with the increased alertness of doctors regarding this pathology, as well as with the improvement of laboratory diagnostics. It is necessary to continue to expand doctors' knowledge about this disease, since the flow of children whose parents bring to the immunologist with complaints of frequent illnesses is increasing from year to year.

During this work, 235 children and 32 adults were also prospectively examined.

The main group consisted of 73 children diagnosed with selective IgA deficiency.

The second group of patients included 153 children with idiopathic thrombocytopenic purpura (ITP). An assessment of the immune status of patients with ITP was carried out in order to identify selective IgA deficiency among them, since this correlation is described in the world literature and the same data were obtained during this study. We did not identify a single child with the absence of IgA among them. Despite the fact that when examining the immune status of patients with ITP, we were unable to identify selective IgA deficiency among them, other minor humoral defects were identified: deficiency of IgG subclasses, infantile hypogammaglobulinemia, partial decrease in IgA.

The third group included 32 adults aged 20 to 54 years, as well as 8 children aged 4 to 10 years, who were close relatives of patients with selective IgA deficiency, whose immune status was assessed in order to search for and describe family cases.

During the survey and analysis of the data obtained, the results described below were obtained.

The ratio of males to females among patients with selective IgA deficiency was approximately the same. 40 boys and 33 girls were examined. This corresponds to the data of world literature.

The peak detection of selective IgA deficiency occurred at the age of 4-7 years. Repeated infectious diseases usually occurred in early age or with the start of attending a preschool institution. As a rule, before going to an immunologist, children accumulated a certain infectious history, since there are certain signs that make it possible to suspect that they have PIDs. And, in addition, even if the study was carried out at an earlier age and revealed the absence of IgA up to 4 years of age, this did not allow us to make an unambiguous diagnosis of PIDS; we could not completely exclude the immaturity of the immunoglobulin synthesis system. Therefore, up to 4 years of age, the diagnosis was made based on questions and dynamic observation was recommended. Hence the interval is 4-7 years, respectively.

The leading complaints when treating children with selective IgA deficiency were frequent respiratory viral infections with an uncomplicated course. The onset of recurrent respiratory diseases, as a rule, occurred before the age of 3 years. This also corresponds to the data of world literature. Since dynamic monitoring of the majority of patients in our study was carried out for a long time, for several years, sometimes before the patient transitioned to adulthood, it can be argued that with age, the frequency and severity of infections decreased. Presumably this occurred due to a compensatory increase in antibodies of the IgG1 and IgG3 subclasses, IgM, but this issue requires further study. The second most common complaint upon treatment was frequent acute respiratory viral infections, accompanied by complications. The frequency of complicated, atypical acute respiratory viral infections with age in our patients, as shown by dynamic observation, also decreased.

Among the spectrum of infectious diseases in patients with selective IgA deficiency, the leading place was occupied by infectious diseases of the ENT organs and lower respiratory tract infections. This is due to the fact that a decrease in secretory IgA, which is part of local immunity, leads to easy infection and proliferation of microorganisms on mucous membranes, which are most vulnerable to contact with infectious diseases transmitted by airborne droplets.

In the spectrum of non-infectious diseases, an obvious correlation has been identified with autoimmune diseases, which are the most important manifestations of selective IgA deficiency, in particular with idiopathic thrombocytopenic purpura (1.5-2 per 100 thousand).

Of the autoimmune diseases in patients with selective IgA deficiency, the most common were juvenile rheumatoid arthritis (4 times), chronic idiopathic thrombocytopenic purpura (3 times), and autoimmune hepatitis (3 times). In addition, according to world literature, patients with selective IgA deficiency have an increased frequency of autoimmune conditions among their immediate family. But, according to our research, their number did not exceed the general population values.

Frequency atopic diseases among patients with selective IgA deficiency was significantly higher than in the population (Table 4). Only the frequency of allergic rhinitis is comparable to the general population. Similar observations are reflected in a number of previous studies. It cannot be said that allergic diseases in most patients with IgA deficiency are more severe than in people without this immunological defect. However, the high prevalence of atopy gives rise to the question of conducting an immunological examination in order to identify forms of selective IgA deficiency, which have not yet manifested themselves clinically. Although this may not have a decisive role in the approach to therapy for the current atopic condition, it will help to make a timely diagnosis and reduce possible risks for people who have selective IgA deficiency.

When analyzing repeated immunograms during dynamic observation in children with selective IgA deficiency, due to persistent changes in laboratory parameters, two large groups of patients were identified. In group A, there was an absence of IgA without any other changes. In group B, the absence of IgA was combined with a persistent increase in the level of IgG. A comparative analysis of these groups of patients was carried out.

The age of onset of clinical manifestations in these groups did not differ significantly.

It was found that in patients with selective IgA deficiency, an increase in IgG levels correlates with recurrent infectious diseases of the skin and soft tissues. This issue requires further study.

When comparing these groups of patients, no significant differences in the spectrum of allergopathology were identified.

During the work, the immune status was assessed in 20 families of patients with selective IgA deficiency. Four familial cases were identified. In addition, a detailed family history was collected. Among adult relatives with a burdened infectious history who were able to undergo examination, there were certain disorders of humoral immunity. Accordingly, when minor humoral defects are detected (in particular, selective IgA deficiency), examination of close relatives, especially in the presence of a burdened infectious history, is mandatory.

Due to the fact that selective IgA deficiency among children in the “frequently ill children” follow-up group is much more common than in the general pediatric population, practicing pediatricians need to be wary of this disease. It is not always easy to suspect it, since clinical manifestations are very variable: from asymptomatic forms to recurrent bacterial infections with the need for frequent antibiotic therapy. It is recommended to expand the knowledge of pediatricians and narrow specialists outpatient and inpatient level about minor defects of the humoral immunity.

Since among patients with selective IgA deficiency there is a significantly higher incidence of allergic pathology (bronchial asthma, atopic dermatitis, food allergies), a higher incidence of autoimmune diseases and hematological diseases, as well as the incidence of chronic diseases (ENT organs, genitourinary system, gastrointestinal tract), than in the population, its identification is mandatory in order to provide complete and timely medical care to patients.

It is recommended to refer children with a burdened infectious history, patients with hematological and autoimmune diseases for consultation with an immunologist/immunological examination, and to conduct a screening examination of the level of total IgA in patients with allergic diseases.

The study found that in the majority of children with selective IgA deficiency, there was a correlation between the presence of autoimmune pathology and a persistent increase in IgG in repeated immunograms. No such correlation has been established for other diseases. Such changes in indicators are a risk factor for the development of autoimmune pathology in a child and require special attention.

Despite the fact that a correlation between the presence of a family history of selective IgA deficiency and the severity of clinical manifestations in patients has not been established, for these patients, examination of close relatives, especially in the presence of a burdened infectious history, is mandatory.

Literature

Hammarstrom L., Lonnqvist B., Ringden O., Smith C. I., Wiebe T. Transfer of IgA deficiency to a bone-marrow-grafted patient with aplastic anemia // Lancet. 1985; 1 (8432): 778-781.
Latiff A. H., Kerr M. A. The clinical significance of immunoglobulin A deficiency // Annals of Clinical Biochemistry. 2007; 44 (Pt 2): 131-139.
Al-Attas R. A., Rahi A. H. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia // Journal of Clinical Immunology. 1998; 18 (5): 368-371.
Carneiro-Sampaio M. M., Carbonare S. B., Rozentraub R. B., de Araujo M. N., Riberiro M. A., Porto M. H. Frequency of selective IgA deficiency among Brazilian blood donors and healthy pregnant women // Allergology Immunopathology (Madr). 1989; 17 (4): 213-216.
Ezeoke A.C. Selective IgA deficiency (SIgAD) in Eastern Nigeria // African Journal of Medicine and Medical Sciences. 1988; 17 (1): 17-21.
Feng L. Epidemiological study of selective IgA deficiency among 6 nationalities in China // Zhonghua Yi Xue Za Zhi. 1992; 72 (2): 88-90, 128.
Pereira L. F., Sapina A. M., Arroyo J., Vinuelas J., Bardaji R. M., Prieto L. Prevalence of selective IgA deficiency in Spain: more than we thought // Blood. 1997; 90(2):893.
Wiebe V., Helal A., Lefranc M. P., Lefranc G. Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E) // Human Genetics. 1994; 93(5):5.

L. A. Fedorova*,
E. S. Pushkova*
I. A. Korsunsky**, 1,candidate medical sciences
A. P. Prodeus*,Doctor of Medical Sciences, Professor

* Federal State Budgetary Educational Institution of Higher Education First Moscow State Medical University named after. I. M. Sechenova Ministry of Health of the Russian Federation, Moscow
** Federal State Budgetary Educational Institution of the Russian National Research University named after. N. I. Pirogova, Moscow

Among the known immunodeficiency conditions, selective immunoglobulin A (IgA) deficiency is the most common in the population. In Europe, its frequency is 1/400-1/600 people; in Asia and Africa, the frequency of occurrence is slightly lower.

Pathogenesis of selective immunoglobulin A deficiency

The molecular genetic basis of IgA deficiency is still unknown. It is assumed that the pathogenesis of the defect lies in a functional defect in B cells, as evidenced, in particular, by a decrease in IgA-expressing B cells in patients with this syndrome. It has been shown that in these patients, many IgA-positive B lymphocytes have an immature phenotype, expressing both IgA and IgD. This is likely due to a defect in factors influencing the functional aspects of switching the expression and synthesis of IgA B cells. There may be defects in both the production of cytokines and disturbances in the response of B cells to various mediators. immune system. The role of cytokines such as TGF-b1, IL-5, IL-10, as well as the CD40-CD40 ligand system is considered.

Most cases of IgA deficiency occur sporadically, but there are also familial cases where the defect can be traced over many generations. Thus, 88 familial cases of IgA deficiency are described in the literature. Autosomal recessive and autosomal dominant forms of inheritance of the defect, as well as an autosomal dominant form with incomplete expression of the trait, have been noted. In 20 families, different members had both selective IgA deficiency and common variable deficiency (CVID), which suggests a common molecular defect in these two immunodeficiency states. Recently, researchers have become increasingly convinced that selective IgA deficiency and CVID are phenotypic manifestations the same thing, not yet identified, genetic defect. Due to the fact that the gene affected by IgA deficiency is not known, several chromosomes are being studied whose damage may presumably be involved in this process.

The main attention is paid to chromosome 6, where the genes of the major histocompatibility complex are located. 8 Some studies indicate the involvement of MHC class III genes in the pathogenesis of IgA deficiency.

Deletions of the short arm of chromosome 18 occur in half of the cases of IgA deficiency, but the exact location of the defect in most patients is not described. In other cases, studies have shown that the location of the chromosome arm 18 deletion does not correlate with the phenotypic severity of the immunodeficiency.

Symptoms of selective immunoglobulin A deficiency

Despite the high prevalence of such immunodeficiency as Selective IgA deficiency, often people with the defect do not have clinical manifestations. This is probably due to the different compensatory capabilities of the immune system, although today this question remains open. With clinically pronounced selective IgA deficiency, the main manifestations are bronchopulmonary, allergic, gastroenterological and autoimmune diseases.

Infectious symptoms

Some studies indicate that respiratory tract infections are more common in patients with IgA deficiency and reduced or absent secretory IgM. It cannot be ruled out that only the combination of IgA deficiency and one or more IgG subclasses, which occurs in 25% of cases in patients with IgA deficiency, leads to serious bronchopulmonary diseases.

The most common diseases associated with IgA deficiency are infections of the upper and lower sections respiratory tract. Basically, the causative agents of infections in such cases are bacteria with low pathogenicity: Moraxella catharalis, Streptococcus pneumonia, Hemophilus influenzae, often causing otitis, sinusitis, conjunctitis, bronchitis and pneumonia in these patients. There are reports that clinical manifestation of IgA deficiency requires a deficiency of one or more IgG subclasses, which occurs in 25% of cases of IgA deficiency. Such a defect leads to serious bronchopulmonary diseases, such as frequent pneumonia, chronic obstructive pulmonary diseases, chronic bronchitis, bronchiectasis. The most unfavorable is considered to be a combined deficiency of IgA and IgG2 subclass, which, unfortunately, is the most common.

Patients with selective IgA deficiency often suffer from various gastrointestinal diseases of both infectious and non-infectious origin. Thus, infection is common among these patients Gardia Lamblia(giardiasis). Other intestinal infections are also common. Probably, a decrease in secretory IgA, which is part of local immunity, leads to more frequent infection and proliferation of microorganisms in the intestinal epithelium, as well as to frequent reinfection after treatment. adequate treatment. Consequence chronic infection intestines is often lymphoid hyperplasia, accompanied by malabsorption syndrome.

Gastrointestinal lesions

Lactose intolerance is also more common in selective IgA deficiency than in the general population. Various diarrheas associated with IgA deficiency, nodular lymphoid hyperplasia and malabsorbcil are usually difficult to treat.

The frequent combination of celiac disease and IgA deficiency is noteworthy. Approximately 1 in 200 patients with celiac disease have this immunological defect (14,26). This association is unique, as celiac enteropathy has not yet been found to be associated with any other immunodeficiencies. A combination of IgA deficiency with autoimmune diseases of the gastrointestinal tract has been described. Conditions such as chronic hepatitis, biliary cirrhosis, pernicious anemia, ulcerative colitis and enteritis.

Allergic diseases

Most clinicians believe that IgA deficiency is accompanied by an increased frequency of almost the entire spectrum allergic manifestations. These are allergic rhinitis, conjunctivitis, urticaria, atopic dermatitis, bronchial asthma. Many experts argue that bronchial asthma in these patients has a more refractory course, which may be due to the development of frequent infectious diseases in them, aggravating asthma symptoms. However, no controlled studies have been conducted on this topic.

Autoimmune pathology

Autoimmune pathology affects not only gastrointestinal tract patients with IgA deficiency. Often these patients suffer rheumatoid arthritis, systemic lupus erythematosus, autoimmune cytopenias.

Anti-IgA antibodies are found in patients with IgA deficiency in more than 60% of cases. The etiology of this immune process is not fully understood. The presence of these antibodies can cause anaphylactic reactions when these patients are transfused with IgA-containing blood products, but in practice the frequency of such reactions is quite low and is about 1 per 1,000,000 blood products administered.

Diagnosis of selective immunoglobulin A deficiency

When studying humoral immunity in children, one often encounters a reduced level of IgA against the background of normal levels of IgM and IgG. Available transient IgA deficiency, in which serum IgA levels are usually shown to be in the range of 0.05-0.3 g/l. More often, this condition is observed in children under 5 years of age and is associated with the immaturity of the immunoglobulin synthesis system.

At partial IgA deficiency The level of serum IgA, although lower than age-related fluctuations (less than two sigma deviations from the norm), still does not fall below 0.05 g/l. Many patients with partial IgA deficiency have normal levels of secretory IgA in saliva and are clinically healthy.

As noted above, selective IgA deficiency is said to occur when serum IgA levels are below 0.05 g/L. Almost always in such cases a decrease in secretory IgA is determined. The content of IgM and IgG may be normal or, less commonly, elevated. A decrease in individual IgG subclasses, especially IgG2 and IgG4, is also common.

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. Possible neutropenia, thrombocytopenia and hemolytic anemia. 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 synthesis and secretion 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 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 can be combined with IgA deficiency, should be excluded.

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%), usually observed at the age of 3-4 months, continues. The IgG level remains low (often below 200 mg%), and the concentrations of IgM and IgA are within normal limits or reduced. Due to a deficiency of antibodies, such children are susceptible to repeated bacterial pneumonia in the period between the disappearance of maternal IgG (at the age of 6 months) and the beginning of its synthesis (18-24 months). With transient hypogammaglobulinemia, infections are milder than in patients who are unable to produce specific antibodies throughout their lives. The level of specific antibodies when immunized 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 noticeable decrease in the levels of IgG 2 and IgG 3 in the serum against the background normal level 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) Replacement therapy immunoglobulin- 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 if necessary large doses IgG (400-500 mg/kg every 3-4 weeks). The plasma IgG level should be greater than 600 mg%. Sometimes an increase in dose or more is indicated to prevent infections. frequent use drug. Whenever side effects(fever, chills, nausea) reduce the frequency of administration, and then pre-prescribe paracetamol or aspirin and diphenhydramine.

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

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. Not yet back to normal cellular immunity, 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) In case of adenosine deaminase deficiency on radiographs chest, pelvis and spine, bone changes are visible.

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) For severe immunodeficiencies (severe combined immunodeficiency, Omen and Wiskott-Aldrich syndromes), transplantation is necessary bone marrow. 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) Brothers and sisters of children with severe combined immunodeficiency should be isolated from the moment of birth and examined to identify 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 occurs frequently 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 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 an immediate request for medical care impossible, parents are provided with oral antibiotics, which should be given to the child when 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 variants are characterized by a low level of 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

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? A referral for an IgA immunoglobulin test can be received from a doctor for both children and adults. So what can this indicator tell the doctor?

What is immunoglobulin A?

Immunoglobulin A is a clear indicator of the state of humoral immunity. This protein can be contained in the body in serum and secretory fractions (both in the blood and in the secretions of the glands). The whey fraction provides local immunity and is 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, and 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 a deficiency of the 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 suffer from 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 still clean water.

Half an hour before the analysis, you should not be very nervous or undergo physical activity. Therefore, if a child donates blood, the parents’ task is to ensure that within the specified time frame he behaves calmly and does not worry about donating blood. You should explain in a calm voice that the procedure is quick and painless, and 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 produced, among other things, 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, renal failure, drugs that lower immunity and different kinds irradiation.

Factors that increase immunoglobulin A levels include certain medications (mainly antipsychotics, anticonvulsants, antidepressants and oral contraceptives), vaccinations given less than 6 months ago, and excessive physical, mental and emotional stress immediately before donating blood.

In some cases, immunoglobulin A deficiency is associated with a specific feature of the patient’s body - it produces antibodies to its own IgA protein. Such patients are at high risk of developing 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 in the early stages). The normal level of immunoglobulin A in children under one year of age 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 can be associated both with the individual characteristics of the body and with the action of any irritants and vary slightly even within one day.

If immunoglobulin A is elevated

If the immunoglobulin A level is outside the limits 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 caused by various neoplasms, including malignant ones.

A high concentration of IgA can be shown in cystic fibrosis, liver diseases, and systemic autoimmune diseases. The lifespan of immunoglobulins of this class is approximately 6-7 days, and the detection of an increased concentration of 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 in 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 when exposed to 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 random mutation), long-term stress, poor social conditions (in particular, malnutrition), poisoning with hazardous substances and cancer.

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 an adequate and complete picture of the patient’s condition, in addition to the 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 take tests for the general blood count, leukocyte count, ESR, protein fractions in serum. If the attending physician has reason to suspect any specific disease, then other, additional tests are prescribed at his discretion. In other words, the analysis for IgA content itself is not very informative; it is of value only when included in a full examination.

Along with hypogammaglobulinemia, which can manifest itself in the form of immunodeficiency of the three main classes of Ig, conditions associated with selective deficiency of one of the Ig classes or with 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, but this 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) complete absence typical B cells, or loss or “masking” of a B cell marker (about 25% of all cases);

B) B cells are present, but do not transform into Ig-producing cells of obvious T cell deficiency (polyclonal activators are ineffective - endogenous defect);

B) 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;

D) 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 in selective IgA deficiency indicate that suppressor cells may differ in their ability to cause deficiency of a certain class of Ig (specific T suppressor cells). 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 deficiency, recurrent upper respiratory tract infections are noted, however, as with selective IgG3, IgG1 and IgG2 deficiency, 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 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 history showed that decreased Ig production may be an inherited trait. In addition, in some cases, IgG deficiency may be the result of infection of the fetus by the rubella virus.

Histological examination 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 found 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 partial violation synthesis of Ig molecules. When discussing the question of the combination of IgG deficiency with high levels of IgM, most researchers believe that in this case the mechanism is disrupted feedback between the synthesis of IgM and IgG. Globulin replacement therapy in some cases led to normalization of IgM levels. Experimental model this state reproduced on chicks 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. The lymph nodes demonstrate a violation 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. It is somewhat 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.

Selective IgE deficiency. Determination of IgE concentration has become possible only in recent years. This is probably the reason why IgE deficiency has been described in only a few clinical cases. The first reports appeared of patients with severe infectious lesions of the mucous membranes. Screening of normal sera made it possible to establish that IgE deficiency is also characteristic of practically healthy individuals. Ataxia-telangiectasia in 70-80% of cases is accompanied by IgE deficiency (often in combination with IgA deficiency), with “selective” IgA deficiency - in approximately 40%. In patients with congenital or acquired hypogammaglobulinemia (impaired synthesis), IgE deficiency is observed in even more than 90% of cases.

Selective IgM deficiency is second in frequency after selective IgA deficiency. Low IgM levels may be an inherited trait. The cause of the disease is associated with a violation of the immunoregulation mechanism and some defects in the structure of IgM. Among the characteristic differences, the first thing to mention is the body’s low resistance to bacterial and viral infections. Interpretation is quite difficult, since the production of IgM is a normal transition step to the secretion of Ig of this class. In this case, this phase, controlled by a specific gene arrangement, is suppressed or skipped. Among concomitant infections, meningococcal sepsis should be especially mentioned. Secondary IgM deficiency has been described in gluten enteropathy. If you follow an appropriate diet, the process becomes reversible.

Giedion-Scheidegge disease. With this anomaly, IgA and IgM are completely absent, while the concentration of IgG is normal or slightly reduced. In none of the described cases was there an increased sensitivity to infectious diseases. In patients with normal IgG levels, a partial functional defect was still found. Already in the first publication, the absence of an immune response to certain antigens was indicated, which was called “immunoparesis.” This observation, as well as the fact that most patients with selective IgA or IgM deficiency were resistant to infectious lesions, indicate that IgG plays a decisive role in protective immunity and that it can functionally compensate for the deficiency of Ig of other classes. When biopsy of lymph nodes, unequal data were obtained: in some cases the histological picture was normal, in other patients the absence of plasma cells and germinal centers was noted.

L-chain defect. In this disease, the production of x-L chains is impaired. In some cases, the defect can be inherited. Thus, in one case, the corresponding genes were present, but mRNA was absent. A similar violation of the A- or two variants of L-chains has not yet been described. The absence of one of the L-chain variants usually does not lead to noticeable clinical manifestations, since the Ig concentration does not decrease to a critical level, however, this disorder is often combined with other pathological processes. A sign of a defect in L-chains is an imbalance in the system.