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TNF 拮抗剂治疗慢性炎症性风湿病患者 8 年内 T 细胞效应功能的变化。

Changes in T cell effector functions over an 8-year period with TNF antagonists in patients with chronic inflammatory rheumatic diseases.

机构信息

Department of Public Health and Infectious Diseases, 'Sapienza' University, Rome, Italy.

Department of Internal Medicine and Medical Specialties, Rheumatology Unit, 'Sapienza' University, Rome, Italy.

出版信息

Sci Rep. 2018 May 18;8(1):7881. doi: 10.1038/s41598-018-26097-x.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7d/5959893/340eac9d8d6c/41598_2018_26097_Fig1_HTML.jpg

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