Progressive B Cell Loss in Revertant X-SCID
Published in Journal of Clinical Immunology, 2020
Recommended citation: Lin CH, Kuehn HS, Thauland TJ, Lee CM, De Ravin SS, Malech HL, Keyes TJ, Jager A, Davis KL, Garcia-Lloret MI, Rosenzweig SD, Butte MJ. (2020). "Progressive B Cell Loss in Revertant X-SCID." Journal of Clinical Immunology. 40: 1001-1009 https://link.springer.com/article/10.1007/s10875-020-00825-3
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.