Epstein–Barr virus-associated T/NK-cell lymphoproliferative diseases with heterozygous IL10RA variants: two cases with pedigree analysis and a literature review

Objective To summarise the clinical and familial characteristics of two patients with Epstein–Barr virus (EBV)-associated T/NK-cell lymphoproliferative diseases carrying heterozygous IL10RA variants and to explore their potential genetic significance. Methods We retrospectively analysed the clinical courses, pathological findings, flow cytometry results, EBV detection in sorted cell populations, genetic testing results, and familial segregation data of the two patients, supplemented by a review of the relevant literature. Results Patient 1 was a 34-year-old man who presented with fever, gastrointestinal bleeding, and multiple colonic ulcers. EBV was predominantly detected in NK cells, followed by persistent expansion of abnormal NK cells, bone marrow involvement, and progression to NK/T-cell lymphoma complicated by haemophagocytic lymphohistiocytosis. Genetic testing identified a heterozygous IL10RA c.85 C>G (p.Pro29Ala) variant, which was also detected in his mother and one sister. Patient 2 was a 32-year-old man with long-standing hepatosplenomegaly, cytopenia, and abnormal liver function. Histopathological examination and EBV testing of sorted cell populations indicated predominant T-cell involvement, with concurrent NK-cell involvement. He carried a heterozygous IL10RA c.301 C>T (p.Arg101Trp) variant, which was also identified in his mother. The p.Pro29Ala variant is currently classified as a variant of uncertain significance, whereas p.Arg101Trp is a known pathogenic allele associated with autosomal recessive IL10RA -related disease. Conclusion Both adult patients with EBV-associated T/NK-cell lymphoproliferative diseases carried a single heterozygous missense variant in IL10RA . However, the same variants were also present in family members without a similar phenotype, and the available evidence is insufficient to establish a direct causal relationship. IL10RA genetic variation warrants further investigation as a potential host susceptibility factor for EBV-associated T/NK-cell diseases.