De Winter Liesbeth M, Hansen Wendy L J, van Steenbergen Hanna W, Geusens Piet, Lenaerts Jan, Somers Klaartje, Stinissen Piet, van der Helm-van Mil Annette H M, Somers Veerle
Hasselt University, Biomedical Research Institute, and transnationale Universiteit Limburg, School of Life Sciences, Hasselt, Belgium.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Rheumatology (Oxford). 2016 Aug;55(8):1431-6. doi: 10.1093/rheumatology/kew198. Epub 2016 Apr 19.
Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA.
Screening for antibodies against novel UH peptides UH-RA.1, UH-RA.9, UH-RA.14 and UH-RA.21, was performed in two large independent cohorts. Peptide ELISAs were developed to screen for the presence of antibodies to UH-RA peptides. First, 292 RA patients (including 39 early patients), 90 rheumatic and 97 healthy controls from UH were studied. Antibody reactivity to two peptides (UH-RA.1 and UH-RA.21) was also evaluated in 600 RA patients, 309 patients with undifferentiated arthritis and 157 rheumatic controls from the Leiden Early Arthritis Clinic cohort.
In both cohorts, 38% of RA patients were seronegative for RF and ACPA. Testing for autoantibodies to UH-RA.1 and UH-RA.21 reduced the serological gap from 38% to 29% in the UH cohort (P = 0.03) and from 38% to 32% in the Leiden Early Arthritis Clinic cohort (P = 0.01). Furthermore, 19-33% of early RA patients carried antibodies to these peptides. Specificities in rheumatic controls ranged from 82 to 96%. Whereas antibodies against UH-RA.1 were related to remission, anti-UH-RA.21 antibodies were associated with inflammation, joint erosion and higher tender and swollen joint counts.
This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA.
尽管近期在类风湿关节炎（RA）诊断生物标志物的发现方面取得了进展，但仍有超过三分之一的RA患者（早期疾病患者中这一比例更高）在无类风湿因子（RF）或抗环瓜氨酸肽抗体（ACPA）的情况下发病。本研究的目的是证实早期和血清阴性RA患者中存在针对哈瑟尔特大学（UH）新肽段的先前已鉴定的自身抗体。
在两个大型独立队列中对针对新型UH肽段UH-RA.1、UH-RA.9、UH-RA.14和UH-RA.21的抗体进行筛查。开发了肽酶联免疫吸附测定（ELISA）来筛查针对UH-RA肽段的抗体。首先，研究了来自UH的292例RA患者（包括39例早期患者）、90例风湿性疾病患者和97例健康对照。还在来自莱顿早期关节炎诊所队列的600例RA患者、309例未分化关节炎患者和157例风湿性疾病对照中评估了对两种肽段（UH-RA.1和UH-RA.21）的抗体反应性。
在两个队列中，38%的RA患者RF和ACPA血清学阴性。在UH队列中，检测针对UH-RA.1和UH-RA.21的自身抗体使血清学阴性率从38%降至29%（P = 0.03），在莱顿早期关节炎诊所队列中从38%降至32%（P = 0.01）。此外，19%至33%的早期RA患者携带针对这些肽段的抗体。风湿性疾病对照中的特异性范围为82%至96%。针对UH-RA.1的抗体与缓解相关，而抗UH-RA.21抗体与炎症、关节侵蚀以及更高的压痛和肿胀关节计数相关。
本研究证实了血清阴性和早期RA患者中存在针对新型UH-RA肽段的抗体反应性。这可能会加强当前的诊断方法，并改善RA的早期诊断和干预。
