Croxford Allyson M, Whittingham Senga, McNaughton Donald, Nandakumar Kutty Selva, Holmdahl Rikard, Rowley Merrill J
Monash University, Clayton, Victoria, Australia.
Arthritis Rheum. 2013 Mar;65(3):650-9. doi: 10.1002/art.37805.
Murine collagen antibody-induced arthritis (CAIA), like collagen-induced arthritis, has clinical and immunopathologic features that parallel those in human rheumatoid arthritis (RA). This study was undertaken to examine the effects of autoantibodies to type II collagen (CII) on articular cartilage in the paws of mice, under conditions in which other factors that may influence joint pathology could be excluded.
Mice of 2 different strains, B10.QC5δ and the parental strain B10.Q, were injected intravenously with either saline or arthritogenic monoclonal antibodies (mAb) to CII. B10.QC5δ mice lack complement factor C5 and do not develop CAIA when injected with arthritogenic mAb, whereas B10.Q mice have C5 and develop CAIA when administered the mAb and a subsequent injection of lipopolysaccharide. Three days after injection the paws of the mice were examined by standard histologic methods to assess morphologic appearance and proteoglycan loss, and by synchrotron-enhanced Fourier transform infrared microspectroscopy to assess chemical evidence of structural change.
No macroscopic or microscopic signs of inflammation were evident in the mice. However, in contrast to the saline-injected controls, all mAb-injected mice exhibited cartilage damage in all joints, with loss of proteoglycans and collagen, chondrocyte hyperplasia and/or loss, and surface damage in the interphalangeal joints.
The implication of these findings is that an autoimmune response to CII can disrupt articular cartilage, particularly that of the small joints, and the subsequent integrity of the cartilage depends on a balance between breakdown and repair. This has relevance with regard to RA, in which such autoantibodies occur but the inflammatory response may dominate clinically and mask underlying features of the autoimmune response.
小鼠胶原抗体诱导的关节炎（CAIA）与胶原诱导的关节炎一样，具有与人类类风湿关节炎（RA）相似的临床和免疫病理特征。本研究旨在在排除其他可能影响关节病理的因素的条件下，研究抗II型胶原（CII）自身抗体对小鼠爪部关节软骨的影响。
将两种不同品系的小鼠，B10.QC5δ及其亲本品系B10.Q，静脉注射生理盐水或抗CII的致关节炎单克隆抗体（mAb）。B10.QC5δ小鼠缺乏补体因子C5，注射致关节炎mAb后不会发生CAIA，而B10.Q小鼠有C5，注射mAb并随后注射脂多糖后会发生CAIA。注射后三天，通过标准组织学方法检查小鼠的爪子，以评估形态外观和蛋白聚糖损失，并通过同步加速器增强傅里叶变换红外显微光谱法评估结构变化的化学证据。
小鼠未出现明显的宏观或微观炎症迹象。然而，与注射生理盐水的对照组相比，所有注射mAb的小鼠在所有关节均表现出软骨损伤，伴有蛋白聚糖和胶原蛋白丢失、软骨细胞增生和/或丢失以及指间关节表面损伤。
这些发现表明，对CII的自身免疫反应可破坏关节软骨，尤其是小关节的软骨，而软骨的后续完整性取决于分解和修复之间的平衡。这与RA相关，在RA中会出现此类自身抗体，但炎症反应在临床上可能占主导地位并掩盖自身免疫反应的潜在特征。
