Objective For better management of 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 (Better Anti Rheumatic PharmacOTherapy) and TIRA-2 (Swedish acronym for ‘tidiga insatser vid reumatoid artrit’) 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 CCP 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志物


目的 为了更好地管理 RA，需要新的生物标志物来预测不同病程的发展。本研究旨在确定针对关节蛋白质表位的自身抗体，并预测新发 RA 患者的疾病结局。方法 来自瑞典 BARFOT （Better Anti Rheumatic PharmacOTherapy） 和 TIRA-2 （瑞典语首字母缩写词 'tidiga insatser vid reumatoid artrit'） 队列 （n = 1986） 的新发 RA 患者的血清在基于微珠的多重流式免疫测定中筛选针对选定肽 （JointID） 的自身抗体。疾病结局包括布尔缓解 1.0 、关节肿胀和影像学破坏。使用考虑临床因素的多变量 logistic 回归和零膨胀负二项式模型来识别预测预后潜力最强的 JointID。结果 在 12 个月时，对非修饰的 II 型胶原 （COL2） 肽抗体阳性的男性患者预测布尔缓解的敏感性为 42%，特异性为 75%。当不存在针对特异性瓜氨酸软骨寡聚蛋白 （COMP） 肽的抗体并且患者在 6 个月时处于布尔缓解状态时，敏感性为 13%，特异性为 99%。未修饰的 COL2 肽的阳性也使 6 个月和 12 个月时关节肿胀的频率分别降低了 41% 和 33%。CCP 抗体预测关节破坏的特异性低 （58%）。瓜氨酸化形式的 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预测高度特异性的缓解，并结合临床因素，可能指导未来的治疗决策。