Immunoglobulin A deficiency is a group of primary immunodeficiency conditions that are caused by impaired synthesis or accelerated destruction of immunoglobulin molecules of this class. The symptoms of the disease are frequent bacterial infections (especially of the respiratory system and ENT organs), disorders of the gastrointestinal tract, allergies and autoimmune lesions. Diagnosis of immunoglobulin A deficiency is made by determining its amount in blood serum, molecular genetic techniques are also used. Treatment is symptomatic, it comes down to the prevention and timely therapy of bacterial infections and other disorders. In some cases, immunoglobulin replacement therapy is performed.
Immunoglobulin A deficiency is a polyetiological form of primary immunodeficiency, in which there is a lack of this class of immunoglobulins with a normal content of the remaining classes (G, M). The deficiency can be complete, with a sharp decrease in all fractions of globulin A, and selective, with a lack of only certain subclasses of these molecules. Selective immunoglobulin A deficiency is a very common condition, according to some data, its occurrence is 1:400-600. The phenomena of immunodeficiency with a selective deficiency of the compound are quite erased, almost two thirds of patients do not have the disease diagnosed because they do not seek medical help. Immunologists have found that immunoglobulin A deficiency can manifest itself not only with infectious symptoms, patients also often have metabolic and autoimmune disorders. Given this circumstance, it can be assumed that the occurrence of this condition is even higher than previously assumed. Modern geneticists believe that the disease occurs sporadically or is a hereditary pathology, and both an autosomal dominant and an autosomal recessive inheritance pathway can act as a transmission mechanism.
The etiology and pathogenesis of both complete and selective immunoglobulin A deficiencies have not been fully determined at the moment. So far, it has been possible to establish only the genetic and molecular mechanisms of individual forms of the disease. For example, selective deficiency of immunoglobulin A type 2 is caused by mutations of the NFRSF13B gene localized on the 17th chromosome and encoding the protein of the same name. This protein is a transmembrane receptor on the surface of B-lymphocytes, responsible for the recognition of tumor necrosis factor and some other immunocompetent molecules. The compound takes an active part in the regulation of the intensity of the immune response and the secretion of various classes of immunoglobulins. According to molecular studies, a genetic defect of the TNFRSF13B gene, leading to the development of an abnormal receptor, makes certain fractions of B-lymphocytes functionally immature. Such cells, instead of producing optimal amounts of immunoglobulins A, secrete a mixture of classes A and D, which leads to a decrease in the concentration of class A.
Mutations of the TNFRSF13B gene are a common, but far from the only reason for the development of immunoglobulin A deficiency. In the absence of damage to this gene and with the existing clinical manifestations of this type of immunodeficiency, mutations are assumed to be present in the 6th chromosome, where the genes of the main histocompatibility complex (HCGS) are located. In addition, a number of patients with immunoglobulin A deficiency have deletions of the short arm of the 18th chromosome, but it is not yet possible to unambiguously link these two circumstances with each other. Sometimes the lack of class A molecules is combined with a deficiency of immunoglobulins of other classes and a violation of the activity of T-lymphocytes, which forms the clinical picture of general variable immunodeficiency (OVID). Some geneticists suggest that immunoglobulin A and OVID deficiency are provoked by very similar or identical genetic defects.
Immunoglobulin A differs from other related molecules in that it causes the very first stage of nonspecific immunological protection of the body, since it is secreted as part of the secretion of the glands of the mucous membranes. With its lack, it becomes easier for pathogenic microorganisms to penetrate into poorly protected delicate tissues of the mucous membranes of the respiratory tract, gastrointestinal tract and ENT organs. The mechanisms of autoimmune, metabolic and allergic disorders in immunoglobulin A deficiency are still unknown. There is an assumption that its low concentration causes an imbalance in the entire immune system.
All manifestations of immunoglobulin A deficiency in immunology are divided into infectious, metabolic (or gastrointestinal), autoimmune and allergic. Infectious symptoms consist in an increased frequency of bacterial infections of the respiratory tract – patients often have laryngitis, tracheitis, bronchitis and pneumonia, which can take a severe course and be accompanied by the development of complications. In addition, immunoglobulin A deficiency is characterized by a rapid transition of acute inflammatory processes into chronic forms, which is especially indicative of lesions of the ENT organs – patients are often diagnosed with otitis, sinusitis and frontitis. A fairly common combined deficiency of immunoglobulins A and G2 leads to severe obstructive pulmonary lesions.
To a lesser extent, infectious lesions affect the gastrointestinal tract. With a deficiency of immunoglobulin A, there is a slight increase in giardiasis, gastritis and enteritis may be registered. The most characteristic symptoms of this immunodeficiency on the part of the gastrointestinal tract are lactose intolerance and celiac disease (immunity of cereal gluten protein), which, in the absence of nutrition correction, can lead to intestinal villi atrophy and malabsorption syndrome. Ulcerative colitis, biliary cirrhosis of the liver and chronic hepatitis of autoimmune genesis are also often registered among patients with immunoglobulin A deficiency. These diseases are accompanied by abdominal pain, frequent episodes of diarrhea, weight loss and hypovitaminosis (due to impaired absorption of nutrients due to malabsorption).
In addition to the above-described diseases of the gastrointestinal tract, autoimmune and allergic lesions with immunoglobulin A deficiency are manifested by an increased frequency of systemic lupus erythematosus and rheumatoid arthritis. Thrombocytopenic purpura and autoimmune hemolytic anemia are also possible, often with a severe course. Autoantibodies against their own immunoglobulin A are detected in the blood of more than half of the patients, which further aggravates the phenomena of the lack of this compound. In patients with immunoglobulin A deficiency, urticaria, atopic dermatitis, bronchial asthma and other diseases of allergic origin are often detected.
Diagnosis of immunoglobulin A deficiency is based on the patient’s medical history (frequent infections of the respiratory tract and ENT organs, gastrointestinal tract lesions), but the most accurate way to confirm the diagnosis is to determine the amount of serum immunoglobulins of different classes. At the same time, an isolated decrease in the level of this component of humoral immunity below 0.05 g / l may be detected, which indicates its deficiency. Against this background, the level of immunoglobulins G and M remains within the normal range, sometimes a decrease in the G2 fraction is detected. With a partial deficiency of immunoglobulin A, its concentration remains in the range of 0.05-0.2 g /l. When evaluating the results of the analysis, it is important to remember the age–related features of the amount of globulins in blood plasma – for example, the concentration of fraction A 0.05-0.3 g / l in children under 5 years of age is called transient deficiency and may disappear in the future.
Sometimes a partial deficiency of immunoglobulin A is detected, in which its amount in plasma is reduced, but the concentration of the compound in the secretions of the mucous membranes is quite high. No clinical symptoms of the disease are detected in patients with partial deficiency. In the immunogram, attention should be paid to the number and functional activity of immunocompetent cells. With immunoglobulin A deficiency, the number of T- and B-lymphocytes is usually maintained at a normal level, a decrease in the number of T-lymphocytes indicates the possible presence of a general variable immunodeficiency. Among other diagnostic methods, the detection of antinuclear and other autoantibodies in plasma, automatic sequencing of the TNFRSF13B gene and allergological tests play an auxiliary role.
Treatment, prognosis and prevention
There is no specific treatment for this immunodeficiency, in some cases, replacement immunoglobulin therapy is performed. Antibiotics are mainly used to treat bacterial infections, sometimes preventive courses of antibacterial agents are prescribed. It is necessary to correct the diet (exclusion of dangerous products) with the development of food allergies and celiac disease. In the latter case, cereal-based dishes are excluded. Bronchial asthma and other allergic pathologies are treated with conventional drugs – antihistamines and bronchodilators. With severe autoimmune disorders, immunosuppressive drugs are prescribed – corticosteroids and cytostatics.
The prognosis for immunoglobulin A deficiency is generally favorable. In many patients, the pathology is absolutely asymptomatic and does not require special treatment. With an increase in the frequency of bacterial infections, autoimmune lesions and malabsorption disorders (malabsorption syndrome), the prognosis may worsen accordingly to the severity of symptoms. To prevent the development of these manifestations, it is necessary to use antibiotics at the first signs of an infectious process, comply with the rules regarding the diet and diet composition, regular monitoring by an immunologist and doctors of other specialties (depending on concomitant disorders). Caution should be exercised when transfusing whole blood or its components – in rare cases, patients have an anaphylactic reaction due to the presence of autoantibodies to immunoglobulin A in the blood.