Progressive B Cell Loss in Revertant X-SCID.

Journal of Clinical Immunology
Connie H LinManish J Butte

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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Citations

Jun 9, 2021·Human Molecular Genetics·Simone FeursteinLucy A Godley

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Methods Mentioned

BETA
flow cytometry
FACS
biopsy
surgical resection
biopsies

Software Mentioned

Cytobank
R CRAN
CyTOF

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