Germline defects of familial hemophagocytic lymphohistiocytosis-related genes presenting as adult-onset peripheral T-cell lymphoma

Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as , , , and were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of and genes and presented as adult-onset periphera...

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Bibliographic Details
Published in:Frontiers in immunology 2024, Vol.15, p.1365975-1365975
Main Authors: Wei, Chong, Zhao, Danqing, Xue, Song, Cai, Hao, Jia, Congwei, Zhou, Daobin, Zhang, Wei
Format: Article
Language:English
Subjects:
cytotoxic function
familial hemophagocytic lymphohistiocytosis
germline mutation
next-generation sequencing
peripheral T-cell lymphoma
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Summary:Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as , , , and were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of and genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1365975