Development of molecular biological methods for diagnosis and treatment of severe combined immunodeficiency

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Severe combined immunodeficiency (SCID) is an inherited immunodeficiency disease in man, characterized by profound abnormalities of both the cellular and humoral arms of the immune system. Among the classic types of SCID,SCID with a normal number of BETA lymphocytes usually demonstrates an CHI-linked inheritance and now is regarded as common gamma-chain gene defect. Here, we report the characterization of mutations in the common gamma-chain gene of eight unrelated SCID with BETA cells patients. One large deletion, one short deletion, one nonsense mutation and four single missense mutations were identified. Three missense mutations were located near the motifs common to members of the class IOTA cytokine receptor family and a methionine at the beginning of the translation was mutated in remaining one patient.Of these eight patients, five received bone marrow transplantation (BMT). Although three patients developed full TAU-and BETA-cell response after HLA-genotypically identical BMT,antibody response remain absent in two patients who received HLA-partially phenotypically identical BMT.In both cases, patient derived BETA cells remain for a long period. As EB-virus transformed BETA cells from patients produce immunoglobulins in vitro, BETA cells in patients might be in an anagy-like state. The exact mechanism of antibody deficiency after BMT remained to be determined.