Article: article from journal or magazin.
Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency.
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
X-linked severe combined immunodeficiency is a life-threatening disorder caused by mutations in the gene encoding the interleukin-2 receptor gamma chain (IL2RG). Hypomorphic mutations and reversion of mutations in subpopulations of cells can result in variant clinical phenotypes, making diagnosis and treatment difficult. We describe a 5-year-old boy with mild susceptibility to infection who was investigated for a mutation in IL2RG due to persistent natural killer (NK)- and T-cell lymphopenia. A functionally relevant novel T466C point mutation was found in B, NK, and epithelial cells, whereas alpha/beta and gamma/delta T cells showed the normal gene sequence, suggesting reversion of the mutation in a common T-cell precursor. This genetic correction in T cells resulted in a diverse T-cell repertoire and significant immunity despite failure to produce specific antibodies linked to an intrinsic defect of mutant B cells. These observations confirm the potential of revertant T-cell precursors to reconstitute immune function, but questions remain on the longevity of revertant cells implicating the need for careful follow up and early consideration of hematopoietic stem cell transplantation (HSCT).
Antibody Formation/genetics, B-Lymphocytes/immunology, B-Lymphocytes/pathology, Child, Preschool, Epithelial Cells/immunology, Epithelial Cells/pathology, Hematopoietic Stem Cell Transplantation, Humans, Interleukin Receptor Common gamma Subunit/genetics, Interleukin Receptor Common gamma Subunit/immunology, Killer Cells, Natural/immunology, Killer Cells, Natural/pathology, Lymphoid Progenitor Cells/immunology, Lymphoid Progenitor Cells/pathology, Lymphopenia/genetics, Lymphopenia/immunology, Male, Point Mutation, Receptors, Antigen, T-Cell, gamma-delta/genetics, Receptors, Antigen, T-Cell, gamma-delta/immunology, T-Lymphocytes/immunology, T-Lymphocytes/pathology, X-Linked Combined Immunodeficiency Diseases/genetics, X-Linked Combined Immunodeficiency Diseases/immunology
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