Abstract
We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20 years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of the IL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20 years. CyTOF (cytometry time of flight) analysis of bone marrow offered a potential explanation of the B cell failure, with expansions of progenitor populations that suggest a developmental block. Another interesting feature was that the patient bore extensive granulomatous disease and skin cancers that contained T cells, despite severe T cell lymphopenia in the blood. Finally, the patient had a few hundred T cells on presentation but his TCRs comprised a very limited repertoire, supporting the important conclusion that repertoire size trumps numbers of T cells.
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We thank the subject and his family for their willingness to participate in studies.
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We received funding from the Jeffrey Modell Foundation and the NIH.
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CHL, SSD, HLM, MIG-L, and MJB provided patient care. MJB obtained IRB approval. CML prepared histology images. TJK, AJ, and KLD performed CyTOF studies. HSK and SDR performed cytokine studies. CHL, MIG-L, and MJB wrote the manuscript.
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All research on human subjects was performed after written informed consent was obtained for protocols approved by the IRBs of the University of California Los Angeles and the National Institutes of Health.
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Lin, C.H., Kuehn, H.S., Thauland, T.J. et al. Progressive B Cell Loss in Revertant X-SCID. J Clin Immunol 40, 1001–1009 (2020). https://doi.org/10.1007/s10875-020-00825-3
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DOI: https://doi.org/10.1007/s10875-020-00825-3