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Proteomic analysis to define predictors of treatment response to adalimumab or methotrexate in rheumatoid arthritis patients.
The Pharmacogenomics Journal ( IF 2.8 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41397-019-0139-4
Stephanie F Ling 1, 2 , Nisha Nair 1 , Suzanne M M Verstappen 2, 3 , Anne Barton 1, 2 , Hans-Dieter Zucht 4, 5 , Petra Budde 4, 5 , Peter Schulz-Knappe 4 , , Darren Plant 1, 2
Affiliation  

Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study.

中文翻译:

蛋白质组学分析可确定类风湿关节炎患者对阿达木单抗或甲氨蝶呤治疗反应的预测指标。

类风湿关节炎(RA)(一种慢性自身免疫性关节炎)患者的抗瓜氨酸肽抗体(ACPA)的血清阳性与长期疾病预后相关。ACPA已在RA患者中普遍检测,但是还存在其他自身抗体(瓜氨酸化和非瓜氨酸化形式),这些抗体可能会提供有关RA亚型和/或治疗反应的其他信息。我们使用了基于多重珠的376种自身抗体的检测方法,以测试这些自身抗体与RA患者的治疗反应之间的关联。定义了具有相似自身抗体表达的患者群,并且群成员与治疗反应相关。与健康对照相比,RA患者中有34种自身抗体差异表达。瓜氨酸波形蛋白与治疗反应有关。在ACPA阴性RA患者的亚分析中,选择了瓜氨酸化自身抗体与治疗反应相关。ACPA阴性RA患者中更精细的ACPA特异性可能预示了治疗反应,可能代表了未来研究的丰富脉络。
更新日期:2019-12-10
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