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T cell functions of psoriatic arthritis patients are regulated differently by TNF, IL-17A and IL-6 receptor blockades in vitro

医学 外周血单个核细胞 肿瘤坏死因子α 白细胞介素2受体 T细胞 内科学 银屑病性关节炎 白细胞介素 免疫学 内分泌学 细胞因子 受体 白细胞介素2
作者
Smadar Gertel,Ari Polachek,Victoria Furer,David Levartovsky,Haya Sidis,Sara Pel,Daphna Paran,Ori Elkayam
出处
期刊:Clinical and Experimental Rheumatology 卷期号:40 (1): 120-128 被引量:1
标识
DOI:10.55563/clinexprheumatol/jdhe41
摘要

The impact of biologics used in PsA management on T cells is unknown. This study evaluated the effect of tumour necrosis factor-alpha (TNFα), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in PsA patients and healthy controls peripheral blood mononuclear cells (PBMCs).A total of 111 PsA patients and 32 healthy controls were recruited. PBMCs were co-cultured in presence of the biologics. T cell activation and proliferation were analysed by flow cytometry and cytokines in supernatants were measured by ELISA. The effect of biologics on lymphocyte proliferation was determined in response to phytohemagglutinin (PHA).Activated CD4+CD25+ T cells were significantly reduced by adalimumab (ADA) in PsA patients as compared to medium, ixekizumab (IXE), and tocilizumab (TCZ), while in healthy controls, ADA reduced the activated CD4+CD25+ T cells non-significantly. Elevated TNFα and IL-1β levels were produced in supernatants of PsA patients as compared to healthy controls. TNFα, IL-17A, IL-1β, and MMP-3 levels were reduced by ADA compared to medium (p<0.0001, p<0.0004, p<0.04, p<0.04, respectively). IXE reduced IL-17A (p<0.0001) but not the other cytokines. ADA had higher susceptibility to inhibit PHA-induced proliferation in both PsA patients and healthy controls (p<0.03) as compared to IXE and TCZ.Both TNF and IL-17A blockers are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.

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