Ca2+ Entry Channel Deficiency
Calcium mobilization is a key event in the activation process of lymphocytes and nonimmune cells. Two molecules, ORAI1 and STIM1, mediate the function of Ca2+ entry channels. ORAI1 is a ubiquitously expressed protein that constitutes the pore-forming subunits of the Ca2+ release-activated channels located in the cell membrane. STIM1 senses the Ca2+ concentration in the endoplasmic reticulum and activates Ca2+ release-activated channels. Mutations of both the ORAI1 and STIM1 genes in humans result in an autosomal recessive immunodeficiency, the clinical manifestations of which resemble SCID with the additional features of nonprogressive myopathy, ectodermal dysplasia, hepatosplenomegaly, hemolytic anemia, and thrombocytopenia.124,125 Although T-cell development is unaffected, in vitro proliferation of circulating T cells to mitogens and to a combination of phorbol ester and ionomycin is drastically reduced, and the Ca2+ influx following T-cell activation is absent. In spite of hypergammaglobulinemia, specific antibody responses are typically absent.
Cure- Allogeneic hematopoietic stem cell transplantation
Allogeneic hematopoietic stem cell transplantation has been used in some patients to correct the defect