Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs
Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs
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DOI：
10.1136/annrheumdis-2016-209297
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发表时间：
2017-02-01
影响因子：
27.4
通讯作者：
Schett, Georg
中科院分区：
文献类型：
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作者：
Figueiredo, Camille P.;Bang, Holger;Schett, Georg
目的详细分析类风湿关节炎（RA）持续缓解患者对翻译后修饰蛋白的自身抗体反应，并探讨其组成是否影响逐渐减少疾病修饰抗风湿药物（DMARD）治疗时疾病复发的风险。方法对94例RETRO研究患者的基线血清样本进行10种瓜氨酸化、高瓜氨酸化/氨基甲酰化和乙酰化肽，以及未修饰的波形蛋白（对照）和环瓜氨酸肽2 （CCP2）的免疫应答检测。根据自身抗体反应次数（0-1/ 10,2 -5/10和> 5/10）或特异性组（瓜氨酸化，氨甲酰化和乙酰化；0-3）对患者进行分类，并检测其DMARD逐渐减少后复发的风险。人口统计学和疾病特异性参数被纳入多变量logistic回归分析，以确定自身抗体在预测复发中的作用。结果患者的抗修饰蛋白抗体反应存在差异，从识别no（0/10）到识别所有抗原（10/10）。针对瓜氨酸蛋白（51%）、乙酰化鸟氨酸（46%）和乙酰化赖氨酸（37%）的抗体是最常见的亚特异性。复发风险显著（p= 0.011）从18%（0-1/10反应）增加到34%（2-5/10）和55%（> 5/10）。与特异性组（0-3）相比，1个、2个或3个抗体特异性组的复发风险分别从18%（无反应性）显著增加到28%、36%和52% （p= 0.021）。结论抗修饰蛋白抗体应答模式决定了RA逐渐减少DMARD治疗患者疾病复发的风险。
Objective To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy.Methods Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and > 5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse.Results Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p= 0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (> 5/10). With respect to specificity groups (0-3), relapse risk significantly (p= 0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively.Conclusions The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy.