Combined T and B-cell immunodeficiencies

Combined immunodeficiencies are syndromes characterized by the absence or decrease in the number and / or function of T-lymphocytes and marked violations of other components of adaptive immunity. Even with normal B cells in the peripheral blood, their function is usually suppressed, in view of the lack of help from the T cells. The most typical and severe form of combined immunodeficiency states is severe combined immune deficiency (SCID, English severe combined immune deficiency, SCID). Based on the latest classification of immunodeficiency states adopted by IUIS in 2005 in Budapest, Omen syndrome, deficiency of CD40 and CD40L, deficiency of MHC II, ZAP70, CD8 and others are also classified as the group of combined immunodeficiency states. These syndromes are heterogeneous manifestations, many patients have a softer course. Nevertheless, for all these conditions, the damage to the cellular and humoral units of immunity and TSCC is the therapy of the choice of combined immunodeficiencies.

Common manifestations of severe combined immune deficiency

In humans, severe combined immune deficiency was first described in 1950 in Switzerland in several infants with lymphopenia, dying from infections during the first year of life. That is why for many years in the literature there was the expression "Swiss type TKIN". In subsequent years, it was found that severe combined immune deficiency includes many syndromes that are of different genetic nature and different types of inheritance (X-linked in 46% of cases and autosomal recessive in 54%). The overall frequency of SCID is 1:50 000 newborns. At present, the genetic nature of about 15 forms of SCID is known, which, based on differences in the immunological phenotype, can be divided into 5 groups: T-B + NK +, TB-NK +, T-B + NK-, T + B + NK- and T- B-NK-.

The main clinical manifestations of severe combined immune deficiency are practically independent of the genetic defect. For patients with SCI is characterized by early, in the first weeks and months of life, the onset of clinical manifestations of the disease in the form of hypoplasia of lymphoid tissue, persistent diarrhea, malabsorption, infections of the skin and mucous membranes, progressive defeat of the respiratory tract. Infectious agents are bacteria, viruses, fungi, opportunistic microorganisms (primarily Pneumocyctis carini). Cytomegalovirus infection occurs in the form of interstitial pneumonia, hepatitis, enteroviruses and adenovirus cause meningoencephalitis. Very part is found in candidiasis of mucous membranes and skin, onychomycosis. Characteristic is the development of regional and / or generalized BCG infection after vaccination. Against the backdrop of severe infections, there is a backlog in physical and motor development. It should be remembered that even in the presence of severe combined immune deficiency, all the above symptoms do not immediately develop in babies, and within 2-3 months they can grow and develop almost normally, especially if BCG vaccination was not done. Transplacental transfer of maternal lymphocytes can cause symptoms of a "graft versus host" (GVHD) reaction, called a maternal-fetal GVHD in this case. It manifests itself mainly as a cutaneous erythema- azure or papular rash and liver damage.

Omen Syndrome

Omen syndrome is a disease characterized by early (first weeks of life) beginning in the form of exudative rash, alopecia, hepatosplenomegaly, generalized lymphadenopathy, diarrhea, hypereosinophilia, heperimmunoglobulinemia E and increased susceptibility to infections characteristic of combined immunodeficiencies. The treatment of skin manifestations with steroids has a negligible effect. This syndrome differs from other forms of CIN in the absence of lymphopenia.

Principles of therapy for severe combined immune deficiency

Severe combined immune deficiency is an urgent condition in pediatrics. If TKIN is diagnosed within the first month of life, adequate therapy and allogeneic HLA of identical or haploidentical bone marrow transplantation (TKM) or hematopoietic stem cells (TSCC) ensures the survival of more than 90% of patients regardless of the form of immunodeficiency. In the case of a later diagnosis, serious infections develop that are poorly amenable to therapy, and the survival of patients falls sharply.

[1], [2], [3]