阿巴西普可降低银屑病关节炎患者滑膜调节性T细胞的表达。
Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis.
作者信息
Szentpetery Agnes, Heffernan Eric, Gogarty Martina, Mellerick Lisa, McCormack Janet, Haroon Muhammad, Elmamoun Musaab, Gallagher Phil, Kelly Genevieve, Fabre Aurelie, Kirby Brian, FitzGerald Oliver
机构信息
Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland.
Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland.
出版信息
Arthritis Res Ther. 2017 Jul 5;19(1):158. doi: 10.1186/s13075-017-1364-3.
BACKGROUND
The aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA).
METHODS
Biological-treatment-naïve PsA patients with active disease including synovitis of a knee were enrolled in this single-centre, crossover study. Patients were randomised to receive intravenous abatacept 3 mg/kg of body weight or placebo infusion on day 1, 15 and 29; thereafter abatacept 10 mg/kg of body weight was administered every 28 days for 5 months. Clinical data were collected at each visit. Synovial biopsy of the involved knee was obtained at baseline and 2 and 6 months. MRI of the same knee and skin biopsy was performed prior to arthroscopy.
RESULTS
Fifteen patients were recruited. Significant improvements in the joint-related measures were observed; 90% were European League Against Rheumatism criteria responders and 30% achieved psoriasis area severity index (PASI)50 at 6 months. Reduction in synovitis (P = 0.016) and vascularity (P = 0.039) macroscopic scores consistent with decrease in total MRI score (P = 0.016) were noticed. Abatacept decreased the immunohistological expression of FOXP3+ cells (P = 0.027), specifically the expression of CD4+FOXP3+ regulatory T cells (Tregs) (P = 0.008) in the synovium over 6 months. There was no significant clinical or immunohistological change in any of the skin measures.
CONCLUSION
This is the first study assessing synovial and psoriatic skin immunpathological changes following abatacept treatment in PsA. Reduction in Treg expression in the synovium but not in the psoriatic lesion suggests abnormal Treg function in PsA with differential suppressive capacity in the synovium compared to the lesional skin. The results of this study demonstrate that abatacept 10 mg/kg of body weight might be an effective treatment option for joint disease in patients with PsA.
TRIAL REGISTRATION
Irish Health Products Regulatory Authority.
TRIAL REGISTRATION NUMBER
CT 900/489/1 - Abatacept (case number: 2077284, EudraCT Number: 2009-017525-19, Protocol number: 77777). Registered on 12 March 2010.
背景
目的是研究银屑病关节炎（PsA）患者接受阿巴西普治疗时滑膜和皮肤炎症免疫组化表达标志物的变化、临床结局及磁共振成像（MRI）评分。
方法
本单中心交叉研究纳入了初治生物制剂且患有包括膝关节滑膜炎在内的活动性疾病的PsA患者。患者于第1、15和29天随机接受静脉注射3mg/kg体重的阿巴西普或安慰剂输注；此后每28天给予10mg/kg体重的阿巴西普，持续5个月。每次就诊时收集临床数据。在基线、2个月和6个月时获取受累膝关节的滑膜活检样本。在关节镜检查前对同一膝关节进行MRI检查并取皮肤活检样本。
结果
招募了15名患者。观察到关节相关指标有显著改善；90%的患者达到欧洲抗风湿病联盟标准应答，6个月时30%的患者银屑病面积和严重程度指数（PASI）改善达50%。注意到滑膜炎（P = 0.016）和血管形成（P = 0.039）的宏观评分降低，与总MRI评分降低（P = 0.016）一致。阿巴西普在6个月内降低了滑膜中FOXP3+细胞的免疫组化表达（P = 0.027），特别是CD4+FOXP3+调节性T细胞（Tregs）的表达（P = 0.008）。任何皮肤指标均未出现显著的临床或免疫组化变化。
结论
这是第一项评估PsA患者接受阿巴西普治疗后滑膜和银屑病皮肤免疫病理变化的研究。滑膜中Treg表达降低但银屑病皮损中未降低，提示PsA中Treg功能异常，滑膜与皮损中的抑制能力存在差异。本研究结果表明，10mg/kg体重的阿巴西普可能是PsA患者关节疾病的有效治疗选择。
试验注册
爱尔兰健康产品监管局。
试验注册号
CT 900/489/1 - 阿巴西普（病例编号：2077284，欧盟临床试验编号：2009 - 017525 - 19，方案编号：77777）。于2010年3月12日注册。
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