Leu Agelii Monica, Sareila Outi, Lönnblom Erik, Cheng Lei, Forslind Kristina, Hafström Ingiäld, Andersson Maria L E, Kastbom Alf, Sjöwall Christopher, Jacobsson Lennart T H, Kihlberg Jan, Holmdahl Rikard, Gjertsson Inger
Rheumatology and Inflammation Research, Gothenburg University, Gothenburg, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Rheumatology (Oxford). 2025 Apr 1;64(4):2227-2232. doi: 10.1093/rheumatology/keae382.
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.
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.
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%).
Autoantibodies against joint-related proteins at RA diagnosis predict remission with high specificity and, in combination with clinical factors, may guide future treatment decisions.
为了更好地管理类风湿关节炎（RA），需要新的生物标志物来预测不同疾病进程的发展。本研究旨在鉴定针对关节中蛋白质表位的自身抗体，并预测新发RA患者的疾病结局。
在基于微珠的多重流式免疫分析中，对来自瑞典BARFOT（更好的抗风湿药物治疗）和TIRA-2（类风湿关节炎早期干预的瑞典首字母缩写）队列的1986例新发RA患者的血清进行筛选，以检测针对选定肽段（关节标识符）的自身抗体。疾病结局包括布尔缓解1.0、肿胀关节计数和影像学破坏。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鉴定具有最强预测预后潜力的关节标识符。
在12个月时，对未修饰的II型胶原蛋白（COL2）肽抗体呈阳性的男性患者中，布尔缓解的预测敏感性为42%，特异性为75%。当不存在针对特定瓜氨酸化软骨寡聚蛋白（COMP）肽的抗体且患者在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肽呈阳性也分别在6个月和12个月时使肿胀关节的频率降低了41%和33%。抗环瓜氨酸肽（CCP）抗体预测关节破坏的特异性较低（58%）。瓜氨酸化形式的COL2肽和葡萄糖-6-磷酸脱氢酶肽呈阳性以敏感性（39%）为代价提高了特异性（86%）。
RA诊断时针对关节相关蛋白的自身抗体可高度特异性地预测缓解，并且与临床因素相结合，可能指导未来的治疗决策。
