Department of Public Health and Infectious Diseases, 'Sapienza' University, Rome, Italy.
Department of Internal Medicine and Medical Specialties, Rheumatology Unit, 'Sapienza' University, Rome, Italy.
Sci Rep. 2018 May 18;8(1):7881. doi: 10.1038/s41598-018-26097-x.
The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFNγ responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25/CD134 in CD4 compared to CD8 T cells both in patients and controls. The in vitro addition of anti-TNF agents induced a significant decrease of both the IFNγ response and of CD25/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID.
本研究旨在阐明长期抗 TNF 治疗对风湿免疫性炎症性疾病(IMID)患者 T 细胞功能的影响。采用 QuantiFERON-TB Gold In-Tube assay 检测 T 细胞在基线及抗 TNF 药物治疗 1、2、4 和 8 年后 IFNγ的产生情况。在开始生物治疗 8 年后,评估植物血凝素刺激后 T 细胞增殖和表面共表达 CD25/CD134 的情况,以及抗 TNF 治疗对 T 细胞功能的体外影响。招募年龄匹配的健康供体作为对照。除了在第 4 年的测定之外,与基线相比,在每个时间点,定量有丝分裂原诱导的 IFNγ 反应均显著增加。我们发现,与对照组相比,患者的 CD4 T 细胞中 CD25/CD134 的表达增加。体外添加抗 TNF 药物可显著降低 IFNγ 反应和 CD25/CD134 的表达,但对增殖反应的强度无影响。我们的数据为长期抗 TNF 治疗 IMID 患者的安全性提供了生物学依据。