ScholarWorks@성균관대학교

초록

X-linked lymphoproliferative syndrome type 1 (XLP1) is an inborn error of immunity caused by pathogenic variants in SH2D1A and is frequently complicated by Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (LPDs). However, cases of LPD without EBV infection have been reported and remain poorly understood. We investigated tumorigenesis mechanisms through transcriptomic profiling and somatic variant analysis in tumor samples from six patients with XLP1. Pathogenic variants were identified in two: one developed two distinct LPDs harboring CARD11/GNA13 and MECOM variants, while the other carried IRF4, P2RY8, KRAS, and CCND3 variants. Transcriptome analysis of three tumors, compared with diffuse large B cell lymphoma from patients without an underlying immune defect, revealed a distinct expression profile. Gene Ontology analysis showed upregulation of adaptive immune response genes, including various IgH and TCR genes, suggesting polyclonal lymphocyte proliferation. Overall, LPD associated with XLP1 may originate from polyclonal lymphocyte expansion, either in the presence or absence of EBV infection, and subsequently progress to malignancy through somatic variants.