Multiple Reversions of an IL2RG Mutation Restore T cell Function in an X-linked Severe Combined Immunodeficiency Patient
Reversion mosaicism is increasingly being reported in primary immunodeficiency diseases, but there have been few cases with clinically improved immune function. Here, a case is reported of X-linked severe combined immunodeficiency (SCID-X1) with multiple somatic reversions in T cells, which restored sufficient cell-mediated immunity to overcome viral infection. Lineage-specific analysis revealed multiple reversions in T cell receptor (TCR) αβ+ and TCRγδ+ T cells. Diversity of the TCRVβ repertoire was comparable to normal and, furthermore, mitogen-induced proliferation of the patient’s T cells was minimally impaired compared to healthy controls. In vivo and in vitro varicella antigen-specific T cell responses were comparable to those of healthy controls, although a reduced level of T cell receptor excision circles suggested that recent thymic output was low. During long-term evaluation of the patient’s immunologic status, both the number of CD4+ and CD8+ T cells and T cell proliferation responses were stable and the patient remained healthy. This case demonstrates that multiple but restricted somatic reversions in T cell progenitors can improve the clinical phenotype of SCID-X1.
KeywordsSevere combined immunodeficiency reversion multiple
We are grateful to the patient and his family for their participation. We also thank Takeda Pharmaceutical Company (Osaka, Japan) for kindly providing recombinant IL-2.
T.K. performed experiments and wrote the paper. M.S. and Ka.I. performed experiments. R.N. designed the research, wrote the paper and analyzed data. Y.T. wrote the paper and analyzed data. T.M. treated the patient and analyzed data. S.O., Y.M., N.N., Ko.I, S.N., T.W. and A.Y. performed experiments and discussed the research. T.H. and T.N. designed the research.
Conflict of Interests
The authors declare no competing financial interests.
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