Journal of Clinical and Experimental Hematopathology
Online ISSN : 1880-9952
Print ISSN : 1346-4280
ISSN-L : 1346-4280
A sporadic case of CTLA4 haploinsufficiency manifesting as Epstein–Barr virus-positive diffuse large B-cell lymphoma
Hepei YuanMomoko NishikoriChiyoko UedaMasakazu FujimotoTakahiro YasumiYasuyuki OtsukaToshio KitawakiMasahiro HirataHironori HagaHirokazu KaneganeAkifumi Takaori-Kondo
ジャーナル オープンアクセス 早期公開

論文ID: 21026


Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory receptor that plays an essential role in maintaining immune system homeostasis by suppressing T-cell activation. We report a sporadic case of CTLA4 haploinsufficiency in a patient with Epstein–Barr virus-positive diffuse large B-cell lymphoma and subsequent benign lymphadenopathy. A missense mutation in exon 2 of the CTLA4 gene (c.251T>C, p.V84A) was found in the patient’s peripheral blood and buccal cell DNA, but not in her parents’ DNA. CTLA4 expression decreased in the peripheral regulatory T cells upon stimulation, whereas CTLA4 and PD-1-positive T cell subsets increased, possibly to compensate for the defective CTLA4 function. This case suggests that some adult lymphoma patients with no remarkable medical history have primary immune disorder. As immune-targeted therapies are now widely used for the treatment of malignancies, it is increasingly important to recognize the underlying primary immune disorders to properly manage the disease and avoid unexpected complications of immunotherapies.

© 2021 by The Japanese Society for Lymphoreticular Tissue Research

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