Epstein-Barr virus-associated T/NK-cell lymphoproliferative diseases with heterozygous IL10RA variants: two cases with pedigree analysis and a literature review.
- 1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
- 2State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, PR China.
- 3Tianjin Institutes of Health Science, Tianjin 301600, PR China.
Abstract
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.
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BibTeX
@article{yan2026epsteinbarr,
title = {{Epstein-Barr virus-associated T/NK-cell lymphoproliferative diseases with heterozygous IL10RA variants: two cases with pedigree analysis and a literature review.}},
author = {Yixin Yan and Ge Song and Liang Huang and Wenjie Xiong and Yao Yao and Yujia Zhai},
journal = {Global medical genetics},
year = {2026},
month = oct,
doi = {10.1016/j.gmg.2026.100140},
url = {https://europepmc.org/article/MED/42898306},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Epstein-Barr virus-associated T/NK-cell lymphoproliferative diseases with heterozygous IL10RA variants: two cases with pedigree analysis and a literature review.
AU - Yixin Yan
AU - Ge Song
AU - Liang Huang
AU - Wenjie Xiong
AU - Yao Yao
AU - Yujia Zhai
PY - 2026
DA - 2026/10/02
JO - Global medical genetics
DO - 10.1016/j.gmg.2026.100140
UR - https://europepmc.org/article/MED/42898306
AB - 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.
SN - 2699-9404
ER -