Severe combined immunodeficiency: causes, symptoms, diagnosis, treatment
Last reviewed: 23.04.2024
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Severe combined immunodeficiency is characterized by the absence of T-lymphocytes and low, high or normal amounts of B-lymphocytes and natural killers. Most infants develop opportunistic infections during 1 -3 months of life. When making a diagnosis, lymphopenia is important, the absence or very low number of T-lymphocytes, a violation of proliferation of lymphocytes under the influence of the mitogen. Patients should be kept in a protected environment; the only method of treatment is the transplantation of bone marrow stem cells.
Severe combined immunodeficiency (TKID) is the result of mutations of at least 10 different genes, which are manifested by 4 forms of the disease. For all forms, T-lymphocytes are absent (T-); but depending on the form of severe combined immunodeficiency, the number of B-lymphocytes and natural killers may be low, or they are absent (B-, NK-), either normal or high (B +, NK +). But even if the level of B-lymphocytes is normal, then because of the lack of T-lymphocytes they can not function normally. The most common type of inheritance is the X-linked chromosome. With this form, there is no y-chain in the protein molecule of the IL2 receptor (this chain is a component of at least 6 cytokine receptors); this is the most severe form with the phenotype of T-, B +, NK-. Other forms are inherited in an autosomal recessive manner. The two most common forms are the result of adenosine deficiency of ADA deaminase, which leads to apoptosis of the precursors of B-, T-lymphocytes and natural killers; the phenotype of this form is T-, B-, NK-. In another form, the α-chain is deficient in the protein molecule of the IL7 receptor; the phenotype of this form is T-, B +, NK +.
Most children with severe combined immunodeficiency develop candidiasis, pneumonia, and diarrhea by the age of 6 months, leading to impaired development. In many, after the introduction of maternal lymphocytes or blood transfusion, the disease "graft against the host" develops. Other patients live up to 6-12 months. Exfoliative dermatitis may develop as part of the Omenna syndrome. Insufficiency of ADA can lead to abnormalities of the bones.
[Treatment of severe combined immunodeficiency
The diagnosis is based on lymphopenia, low or no T-lymphocytes, lack of lymphocyte proliferation in response to mitogen stimulation, absence of radiological shadow of the thymus, impaired lymphoid tissue development.
All forms of severe combined immunodeficiency are fatal if early diagnosis and treatment is not performed. Supporting treatments may be intravenous immunoglobulin and antibiotics, including the prevention of Pneumocystis jiroveci (formerly P . Carinii ). 90-100% of patients with severe combined immunodeficiency and its forms showed bone marrow stem cell transplantation from HLA-identical sibs, selected according to mixed leukocyte culture. If it is impossible to select an HLA-identical sibs, a haploidentical bone marrow of one of the parents with carefully washed T lymphocytes is used. If severe combined immunodeficiency is diagnosed before the age of 3 months, the survival rate after bone marrow transplantation by any of the above methods is 95%. Pre-implantation chemotherapy is not performed, as the recipient does not have T-lymphocytes, and therefore transplant rejection is impossible. Patients with ADA deficiency who are not shown bone marrow transplantation are injected with polyethylene glycol-modified bovine ADA once or twice a week. Gene therapy is successful in the X-linked form of severe combined immunodeficiency, but can cause T-cell leukemia, which limits the use of this method.