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 severe disorders of other components of the adaptive immunity. Even with a normal content of B-cells in the peripheral blood, their function is usually suppressed due to the lack of help from T-cells. The most typical and severe type of combined immunodeficiency states is severe combined immune deficiency (SCID). Based on the latest classification of immunodeficiency states adopted by IUIS in 2005 in Budapest, the group of combined immunodeficiency states also includes Omen syndrome, CD40 and CD40L deficiency, MHC II, ZAP70, CD8 deficiency and others. These syndromes are characterized by heterogeneity of manifestations, with many patients experiencing a milder course. However, in all these conditions, damage to the cellular and humoral links of immunity is observed, and HSCT is the therapy of choice for combined immunodeficiencies.

General manifestations of severe combined immunodeficiency

In humans, severe combined immunodeficiency was first described in 1950 in Switzerland in several infants with lymphopenia who died of infections during the first year of life. That is why the expression "Swiss type of SCID" was encountered in the literature for many years. In subsequent years, it was revealed that severe combined immunodeficiency includes many syndromes with different genetic origins and different types of inheritance (X-linked in 46% of cases and autosomal recessive in 54%). The overall incidence of SCID is 1:50,000 newborns. Currently, the genetic origin of approximately 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. Patients with SCID are characterized by early, in the first weeks and months of life, onset of clinical manifestations of the disease in the form of lymphoid tissue hypoplasia, persistent diarrhea, malabsorption, skin and mucous membrane infections, progressive damage to the respiratory tract. The causative agents of infections are bacteria, viruses, fungi, opportunistic microorganisms (primarily Pneumocyctis carini). Cytomegalovirus infection occurs in the form of interstitial pneumonia, hepatitis, enteroviruses and adenovirus cause meningoencephalitis. Candidiasis of the mucous membranes and skin, onychomycosis are very common. The development of regional and / or generalized BCG infection after vaccination is typical. Against the background of severe infections, a lag in physical and motor development is observed. It should be remembered that even in the presence of severe combined immunodeficiency, infants do not immediately develop all the above symptoms, and within 2-3 months they can grow and develop almost normally, especially if BCG vaccination has not been done. Transplacental transfer of maternal lymphocytes can cause symptoms of graft-versus-host disease (GVHD), in this case called maternal-fetal GVHD. It manifests itself mainly in the form of cutaneous erythema or papular rash and liver damage.

Omen syndrome

Omen syndrome is a disease characterized by early (first weeks of life) onset of exudative rash, alopecia, hepatosplenomegaly, generalized lymphadenopathy, diarrhea, hypereosinophilia, hyperimmunoglobulinemia E, and increased susceptibility to infections typical of combined immunodeficiencies. Steroid therapy of skin manifestations has little effect. This syndrome differs from other forms of CIN by the absence of lymphopenia.

Principles of therapy for severe combined immunodeficiency

Severe combined immunodeficiency is a pediatric emergency. If SCID is diagnosed within the first month of life, adequate therapy and allogeneic HLA identical or haploidentical bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) ensure survival of more than 90% of patients regardless of the form of immunodeficiency. In case of later diagnosis, severe infections develop that are difficult to treat, and patient survival drops sharply.

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