Grywalska Ewelina, Mielnik Michał, Podgajna Martyna, Hymos Anna, Ludian Jarosław, Rolińska Agnieszka, Gosik Krzysztof, Kwaśniewski Wojciech, Sosnowska-Pasiarska Barbara, Smok-Kalwat Jolanta, Pasiarski Marcin, Stelmach-Gołdyś Agnieszka, Góźdź Stanisław, Roliński Jacek
Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland.
Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland.
Cancers (Basel). 2022 Jan 28;14(3):672. doi: 10.3390/cancers14030672.
Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; = 0.027) and CD86 on CD19+ cells (r = 0.6950; < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling ( < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.
感染爱泼斯坦-巴尔病毒（EBV）会使慢性淋巴细胞白血病（CLL）的预后恶化，但潜在机制尚未明确。我们旨在评估EBV是否通过CTLA-4/CD86信号通路失调影响CLL病程。我们采用聚合酶链反应检测了110例新诊断CLL患者血液中EBV DNA载量。通过流式细胞术评估淋巴细胞上CTLA-4和CD86抗原的表达。此外，通过酶联免疫吸附测定法检测CTLA-4和CD86血清浓度。54%的患者可检测到EBV DNA[EBV(+)]。在EBV(+)患者中，CTLA-4和CD86血清浓度及其在所研究细胞群体上的表达显著高于EBV(-)患者。EBV载量与CLL不良预后标志物以及CD3+淋巴细胞上CTLA-4的表达（r = 0.5339；P = 0.027）和CD19+细胞上CD86的表达（r = 0.6950；P < 0.001）呈正相关。在中位随访期32个月期间，EBV(+)患者更有可能需要治疗或出现淋巴细胞倍增（P < 0.001）。在EBV(+)而非EBV(-)患者中，CTLA-4淋巴细胞表达增加与疾病进展风险升高相关。我们提出，EBV合并感染可能会使CLL患者预后恶化，部分原因是EBV诱导CTLA-4表达上调。
