Objective For better management of rheumatoid arthritis (RA), new biomarkers are needed to predict the development of different disease courses. This study aims to identify autoantibodies against epitopes on proteins in the joints and to predict disease outcome in patients with new onset RA. Methods Sera from new onset RA patients from the Swedish BARFOT and TIRA-2 cohorts (n = 1986) were screened for autoantibodies to selected peptides (JointIDs) in a bead-based multiplex flow immunoassay. Disease outcomes included Boolean remission 1.0, swollen joint count and radiographic destruction. Multivariate logistic regression and zero-inflated negative binomial models that accounted for clinical factors were used to identify JointIDs with the strongest potential to predict prognosis. Results Boolean remission was predicted with 42% sensitivity and 75% specificity in male patients positive for antibodies to a non-modified collagen type II (COL2) peptide at 12 months. When antibodies to a specific citrullinated cartilage oligomeric protein (COMP) peptide were absent and the patient was in Boolean remission at 6 months, the sensitivity was 13% and the specificity 99%. Positivity for the non-modified COL2 peptide also reduced the frequency of swollen joints by 41% and 33% at 6 and 12 months, respectively. Antibodies to cyclic citrullinated peptides (aCCP) predicted joint destruction with low specificity (58%). Positivity for a COL2 and a glucose-6-phosphate dehydrogenase peptide in citrullinated forms increased specificity (86%) at the expense of sensitivity (39%). Conclusion Autoantibodies against joint-related proteins at RA diagnosis predict remission with high specificity and, in combination with clinical factors, may guide future treatment decisions.

中文翻译：

---

关节相关肽的自身抗体作为早期类风湿性关节炎的预测标记


目的 为了更好地治疗类风湿性关节炎（RA），需要新的生物标志物来预测不同病程的发展。本研究旨在鉴定针对关节蛋白质表位的自身抗体，并预测新发 RA 患者的疾病结果。方法 采用基于微珠的多重流式免疫测定法，对来自瑞典 BARFOT 和 TIRA-2 队列 (n = 1986) 的新发 RA 患者的血清进行筛选，以确定针对选定肽 (JointID) 的自身抗体。疾病结果包括布尔缓解 1.0、肿胀关节计数和放射学破坏。使用考虑临床因素的多变量逻辑回归和零膨胀负二项式模型来识别最有可能预测预后的 JointID。结果 12 个月时，未修饰 II 型胶原蛋白 (COL2) 肽抗体呈阳性的男性患者预测布尔缓解的敏感性为 42%，特异性为 75%。当特定瓜氨酸软骨寡聚蛋白 (COMP) 肽的抗体不存在且患者在 6 个月时处于布尔缓解时，敏感性为 13%，特异性为 99%。未修饰的 COL2 肽的阳性结果还使 6 个月和 12 个月时关节肿胀的频率分别降低了 41% 和 33%。环瓜氨酸肽 (aCCP) 抗体预测关节破坏的特异性较低 (58%)。瓜氨酸形式的 COL2 和葡萄糖-6-磷酸脱氢酶肽的阳性增加了特异性 (86%)，但牺牲了敏感性 (39%)。结论 RA 诊断时针对关节相关蛋白的自身抗体可以高度特异性地预测缓解，并结合临床因素，可以指导未来的治疗决策。