Geng Hui, Nandakumar Kutty Selva, Pramhed Anna, Aspberg Anders, Mattsson Ragnar, Holmdahl Rikard
Arthritis Res Ther. 2012 Aug 20;14(4):R191. doi: 10.1186/ar4022.
Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP-specific monoclonal antibodies (mAbs).
B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated and the pathogenicity of mAbs was investigated by passive transfer experiments.
B cell immunodominant epitopes were localized within 4 antigenic domains of the COMP but with preferential response to the epidermal growth factor (EGF)-like domain. Some of our anti-COMP mAbs showed interactions with the native form of COMP, which is present in cartilage and synovium. Passive transfer of COMP-specific mAbs enhanced arthritis when co-administrated with a sub-arthritogenic dose of a mAb specific to collagen type II. Interestingly, we found that a combination of 5 COMP mAbs was capable of inducing arthritis in naive mice.
We have identified the specificities of mAbs to COMP and their contribution to the development of arthritis. These findings will further improve our understanding of the autoantibody mediated immunopathologies occurring widely in rheumatoid arthritis (RA), as well as in other autoimmune disorders.
软骨寡聚基质蛋白（COMP）是软骨的主要非胶原蛋白成分。此前，我们利用COMP开发了一种新的类风湿性关节炎小鼠模型。本研究旨在调查COMP特异性单克隆抗体（mAb）的表位特异性和免疫致病性。
使用哺乳动物表达的全长小鼠COMP以及一组重组小鼠COMP片段，通过一种新型酶联免疫吸附测定法测量COMP分子上的B细胞免疫显性区域。生成了18种针对COMP的mAb，并通过被动转移实验研究了mAb的致病性。
B细胞免疫显性表位定位于COMP的4个抗原结构域内，但对表皮生长因子（EGF）样结构域有优先反应。我们的一些抗COMP mAb显示与软骨和滑膜中存在的COMP天然形式相互作用。当与亚致关节炎剂量的抗II型胶原mAb共同给药时，COMP特异性mAb的被动转移增强了关节炎。有趣的是，我们发现5种COMP mAb的组合能够在未接触过抗原的小鼠中诱发关节炎。
我们已经确定了mAb对COMP的特异性及其对关节炎发展的作用。这些发现将进一步增进我们对类风湿性关节炎（RA）以及其他自身免疫性疾病中广泛发生的自身抗体介导的免疫病理学的理解。
