Mertowska Paulina, Mertowski Sebastian, Kozińska Aleksandra, Sobstyl Małgorzata, Roliński Jacek, Grywalska Ewelina
Department of Experimental Immunology, Medical University of Lublin, Lublin, Poland
Department of Experimental Immunology, Medical University of Lublin, Lublin, Poland.
Pol Arch Intern Med. 2025 May 29;135(5). doi: 10.20452/pamw.16973. Epub 2025 Mar 10.
The immune system protects the body against pathogens, and its dysfunction leads to primary and secondary immunodeficiencies, increasing infection susceptibility. Epstein-Barr virus (EBV) reactivation is linked to immune homeostasis disorders, particularly in common variable immunodeficiency (CVID) and chronic lymphocytic leukemia (CLL). Toll‑like receptor (TLR) pathways play a crucial role in innate immunity, and their deregulation may contribute to immune dysfunction.
This study aimed to assess the impact of EBV reactivation on immune homeostasis, focusing on TLR2, TLR4, TLR7, and TLR9 expression in T and B lymphocyte subpopulations and their soluble forms in CVID and CLL patients.
The study included 60 CVID patients, 60 CLL patients, and 30 healthy controls. EBV antigens, viral DNA levels, T and B lymphocyte immunophenotypes, and serum soluble TLR (sTLR) concentrations were analyzed using flow cytometry and enzyme‑linked immunosorbent assay.
EBV reactivation was detected in 55% of CVID and 60% of CLL patients. These patients showed significant TLR expression disturbances and increased sTLR levels. Notably, TLR7 and TLR9 expression was elevated in CD4+, CD8+ T, and CD19+ B cells, correlating with EBV load and immune dysfunction severity.
EBV reactivation plays a key role in TLR pathway deregulation in CVID and CLL, potentially accelerating disease progression and increasing infection risk. TLR expression and sTLR levels could serve as biomarkers for EBV reactivation, aiding therapeutic strategies to stabilize immune responses.
免疫系统保护机体抵御病原体，其功能失调会导致原发性和继发性免疫缺陷，增加感染易感性。爱泼斯坦-巴尔病毒（EBV）再激活与免疫稳态紊乱有关，尤其是在常见变异型免疫缺陷（CVID）和慢性淋巴细胞白血病（CLL）中。Toll样受体（TLR）通路在固有免疫中起关键作用，其失调可能导致免疫功能障碍。
本研究旨在评估EBV再激活对免疫稳态的影响，重点关注CVID和CLL患者T和B淋巴细胞亚群中TLR2、TLR4、TLR7和TLR9的表达及其可溶性形式。
该研究纳入了60例CVID患者、60例CLL患者和30名健康对照。使用流式细胞术和酶联免疫吸附测定法分析EBV抗原、病毒DNA水平、T和B淋巴细胞免疫表型以及血清可溶性TLR（sTLR）浓度。
在55%的CVID患者和60%的CLL患者中检测到EBV再激活。这些患者表现出明显的TLR表达紊乱和sTLR水平升高。值得注意的是，CD4 +、CD8 + T和CD19 + B细胞中TLR7和TLR9表达升高，与EBV载量和免疫功能障碍严重程度相关。
EBV再激活在CVID和CLL的TLR通路失调中起关键作用，可能加速疾病进展并增加感染风险。TLR表达和sTLR水平可作为EBV再激活的生物标志物，有助于制定稳定免疫反应的治疗策略。
