Selective immunoglobulin deficiency A: symptoms, diagnosis, treatment

Among the known immunodeficiency states, the selective deficiency of immunoglobulin A (IgA) is most common in the population. In Europe, its frequency is 1 / 400-1 / 600 people, in Asian and African countries the frequency of occurrence is somewhat lower.

A selective deficit is considered to be a condition in which the serum IgA level is less than 0.05 g / l with normal quantitative indices of other immunity units.

[1], [2], [3], [4]

Pathogenesis of selective deficiency of immunoglobulin A

The molecular genetic basis of IgA deficiency is still unknown. It is assumed that the pathogenesis of the defect is a functional defect in B cells, which is indicated, in particular, by a decrease in IgA-expressing B cells in patients with this syndrome. It was shown that in these patients many lgA-positive B lymphocytes have an immature phenotype, expressing simultaneously IgA and IgD. This is probably due to a defect in factors affecting the functional aspects of the switching of expression and the synthesis of IgA B cells. There will be defects both in the production of cytokines, and in the response of B cells to various mediators of the immune system. The role of such cytokines 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 family cases are also noted, where the defect is traced in many generations. Thus, 88 family cases of IgA deficiency have been described in the literature. Autosomal recessive and autosomal dominant forms of inheritance of the defect are noted, as well as an autosomal dominant form with incomplete expression of the trait. In 20 families, different members simultaneously had selective IgA deficiency and general variable insufficiency (OVIN), which suggests a common molecular defect in these two immunodeficiency states. Recently, researchers have become increasingly convinced that the selective deficiency of IgA and OBID are phenotypic manifestations the same, as yet unidentified, genetic defect. Due to the fact that the gene that suffers from IgA deficiency is not known, several chromosomes are investigated, the damage of which can supposedly be involved in this process.

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

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

Symptoms of selective deficiency of immunoglobulin A

Despite the high prevalence of such immunodeficiency as Selective IgA deficiency, often people with a defect have no clinical manifestations. This is probably due to various compensatory possibilities of the immune system, although this issue remains open to this day. With clinically expressed selective deficiency of IgA, the main manifestations are broncho-pulmonary, allergic, gastroenterological and autoimmune diseases.

Infectious Symptoms

Some studies note that respiratory infections are more common in patients with IgA deficiency and reduced or absent secretory IgM. It is excluded that only a combination of IgA deficiency and one or more subclasses of IgG, which occurs in 25% of cases in patients with IgA deficiency, leads to severe bronchopulmonary diseases.

The most common diseases associated with IgA deficiency are infections of the upper and lower respiratory tract. In most cases, pathogens are caused by bacteria with low pathogenicity: Moraxella catharalis, Streptococcus pneumonia, Hemophilus influenzae, often causing otitis, sinusitis in these patients , conjunctivitis, bronchitis and pneumonia. There are reports that the clinical manifestation of IgA deficiency requires the deficiency of one or more subclasses of IgG, 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 the combined deficit of the IgA and IgG2 subclass, which, unfortunately, most often occurs.

Patients with selective IgA deficiency often suffer from various gastrointestinal diseases, both infectious and non-infectious. So, among these patients, the infection of Gardia Lamblia (Giardiasis) is common . Other intestinal infections are common. It is likely that a decrease in secretory IgA, which is part of the local immunity, leads to more frequent infection and multiplication of microorganisms in the intestinal epithelium, as well as to frequent reinfection after adequate treatment. The consequence of a chronic infection of the intestine is often lymphoid hyperplasia, accompanied by malabsorption syndrome.

GI tract disorders

Lactose intolerance is also more likely than in the general population to occur with selective IgA deficiency. Various diarrhea associated with IgA deficiency, nodular lymphoid hyperplasia, and malabsorbicle usually do not respond well to treatment.

A frequent combination of celiac disease and IgA deficiency deserves attention. Approximately 1 in 200 patients with celiac disease have this immunological defect (14,26). This association is unique, since there has been no association of gluten enteropathy with any other immunodeficiencies. A combination of IgA deficiency with autoimmune diseases of the gastrointestinal tract is described. Often there are such conditions 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 range of allergic manifestations. This 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 the symptoms of asthma. However, there were no controlled studies on this topic.

[5], [6], [7], [8], [9], [10]

Autoimmune pathology

Autoimmune pathology affects not only the gastrointestinal tract of patients with IgA deficiency. Often these patients suffer from 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 transfusing these patients with IgA-containing blood products, but in practice the frequency of such reactions is small enough and is about 1 per 1,000,000 injected blood products.

[11], [12], [13], [14]

Diagnosis of selective deficiency of immunoglobulin A

In the study of humoral immunity in children, it is often enough to encounter a reduced level of IgA against normal IgM and IgG. Transient IgA deficiency is possible , in which serum IgA is shown, as a rule, are 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.

With partial IgA deficiency, the level of serum IgA, although below the age fluctuations (less than two sigma deviations from the norm), but still does not drop below 0.05 g / l. Many patients with partial IgA deficiency have a normal level of secretory IgA in saliva and are clinically healthy.

As noted above, the selective IgA deficiency is said to be less than 0.05 g / L for serum IgA. Almost always in such cases, depression and secretory IgA is determined. The content of IgM and IgG can be normal or, rarely, increased. Often there is a decrease in individual subclasses of IgG, especially IgG2, IgG4.

[15]

Treatment of selective deficiency of immunoglobulin A

Specific treatment of IgA deficiency is absent, since there are no drugs that activate IgA-producing B cells. Theoretically, infusion of serum IgA or IgA-containing plasma may temporarily correlate IgA deficiency, but one must take into account the high risk of anaphylactic reactions in sensitized patients with anti-IgA antibodies. Patients with severe infectious pathology against the background of IgA deficiency associated with deficiency of IgG subclasses or with a decrease in the specific antibody response to bacterial and vaccinal antigens showed intravenous immunoglobulin with a minimum IgA content or complete absence of IgA.

Noncommunicable diseases in patients with IgA deficiency are treated in the same way as in ordinary patients. For example, patients with systemic lupus erythematosus and IgA deficiency respond well to immunosuppressive therapy. Patients with IgA deficiency and bronchial asthma are treated according to standard schemes. However, among such patients, resistance to therapy is more common, possibly because of the development of concomitant infections.

Forecast

In general, the prognosis of the disease is favorable, life-threatening complications develop infrequently.

[16]