Syndrome of hyperimmunoglobulinemia IgM

Hyperimmunoglobulinemia IgM syndrome is associated with immunoglobulin deficiency and is characterized by a normal or elevated serum IgM level and the absence or decreased amount of other serum immunoglobulins, leading to increased susceptibility to bacterial infections.

Syndrome of hyperimmunoglobulinemia IgM can be inherited on the linked to the X-chromosome or autosomal type. Most of the cases involve a mutation of genes that are localized on the X chromosome and encode proteins (CD154 or CD40 ligands) on the surface of activated Tx. In the presence of cytokines, the normal CD40 ligand interacts with B-lymphocytes and thus signals to them about the need to switch the production of IgM to hyperimmunoglobulinemia IgG, IgA, IgE. When the syndrome of hyperproduction of IgM linked to the X chromosome on T lymphocytes does not function, CD154, and B-lymphocytes do not receive a signal about the need to switch the synthesis of isotypes. Thus, B-lymphocytes produce only IgM; its level can be normal or elevated. Patients with this form of immunodeficiency observed neutropenia and often in early childhood - pneumonia caused by Pneumocystic jiroveci (formerly P . Carinii ). In other words, the clinical manifestations are similar to the agammaglobulinemia linked to the X-chromosome and include recurrent bacterial infections of the paranasal sinuses and lungs during the 1-2 years of life. The susceptibility to Cryptosporidium sp. Lymphoid tissue is weakly expressed, since there are no germinal centers. Many patients die before pubertal age, comforts that live longer, develop cirrhosis or B-cell lymphomas.

At least 4 autosomal recessive forms of the syndrome of hyperimmune-globulinemia IgM are associated with defects of B-lymphocytes. In two of these forms (defective activation-induced cytidine deaminase and uracil DNA glycosylase or uracil DNA deficiency of glycosylase), the level of serum IgM is significantly higher than when linked to the X-chromosome form; there is lymphoid hyperplasia (lymphadenopathy, splenomegaly, hypertrophy of the tonsils), and autoimmune disorders are possible.

The diagnosis is based on clinical manifestations, normal or elevated IgM level, low level or complete absence of other lg. Treatment includes intravenous administration of immunoglobulin at a dose of 400 mg / kg / month. In the case of X-linked chromosome form, granulocyte colony-stimulating factor is also prescribed in case of non-isotropy, and since the prognosis is unfavorable, bone marrow transplantation from HLA-identical sibs is preferable.

Insufficiency of IgA

IgA deficiency is set at an IgA level of less than 10 mg / dl at normal levels of IgG and IgM. This is the most frequent immunodeficiency. In many patients it is asymptomatic, but others develop recurrent infections and autoimmune processes. The diagnosis is based on measuring the level of serum immunoglobulins. Some patients develop a general variable immunodeficiency, others have a spontaneous improvement. Treatment consists in removal from the blood of complexes containing IgA; if necessary, antibiotics are prescribed.

Insufficiency of IgA affects 1/333 of the population. Inherited by autosomal dominant type with incomplete penetrance. Insufficiency of IgA is usually associated with a specific HLA-haplotype, less often with alleles or deletions of genes in the region of MHC class III molecules. IgA deficiency also occurs in the siblings of children with OVID and in some patients it evolves in the OVID. In genetically predisposed patients, the use of drugs such as phenytoin, sulfosalazine, colloidal gold, and D-penicillamine may lead to IgA deficiency.

Symptoms of IgA deficiency

In many patients, the disease is asymptomatic; in others, recurrent infections of the paranasal and lung, diarrhea, allergic conditions or autoimmune disorders (eg celiac disease or inflammatory bowel disease, SLE, chronic active hepatitis) are noted. After the introduction of IgA or immunoglobulin, anti-1gA antibodies can form; anaphylactic reactions to IVIG or other preparations containing IgA may also occur.

The diagnosis is expected in patients with recurrent infections (including giardiasis); anaphylactic reactions to transfusion; if there is a family history of OVID, lack of IgA or autoimmune disorders, as well as those who took drugs, the reception of which can lead to the development of IgA deficiency. The diagnosis is confirmed if the IgA level is <10 mg / dl at normal levels of IgG and IgM, the normal antibody titer in response to vaccination with antigens.

Prognosis and treatment of IgA deficiency

A small number of patients with IgA deficiency develop an OVID; others have a spontaneous improvement. The prognosis worsens in the development of autoimmune processes.

Treatment consists in avoiding products containing IgA, since even a small amount of it leads to the development of an anti-1gA-mediated anaphylactic reaction. If transfusion of erythrocytes is required, then only washed red blood cells or frozen blood products are used. If necessary, antibiotics are used to treat bacterial infections of the ear, paranasal sinuses, lungs, gastrointestinal and urogenital tracts. IVIG is contraindicated, since many patients have antibodies to IgA, and when IVIG is administered more than 99% of IgG, which patients do not need.