Carlsén S, Hansson A S, Olsson H, Heinegård D, Holmdahl R
Section for Medical Inflammation Research, Lund University, Lund, Sweden.
Clin Exp Immunol. 1998 Dec;114(3):477-84. doi: 10.1046/j.1365-2249.1998.00739.x.
In rheumatoid arthritis peripheral cartilaginous joints are inflamed and eroded. One driving factor may be an immune response towards proteins in the cartilage. Here it is shown that cartilage oligomeric matrix protein (COMP), expressed specifically in cartilage, is arthritogenic in the rat. Both native and denatured rat COMP induced severe arthritis in selected rat strains. The arthritis occurred only in peripheral joints which were attacked by an erosive inflammatory process similar to that seen in the human disease. The disease was self-limited and no permanent destruction of joints was seen macroscopically. Disease development appeared to be dependent on an immune response to autologous (rat) COMP and not on cross-reactivity to other cartilage rat collagens (types II, IX and XI). The disease and the immune response to COMP were genetically controlled by the MHC; the RT1u and RT1l haplotypes were more susceptible than the a, c, d, f and n haplotypes. Both LEW and E3 gene backgrounds were highly permissive for disease induction. These findings suggest that the induction of arthritis with rat COMP represents a unique pathogenesis which is controlled by different genes compared with collagen-induced arthritis or adjuvant-induced arthritis.
在类风湿性关节炎中，外周软骨关节会发生炎症和侵蚀。一个驱动因素可能是对软骨中蛋白质的免疫反应。本文表明，在软骨中特异性表达的软骨寡聚基质蛋白（COMP）在大鼠中具有致关节炎作用。天然和变性的大鼠COMP在选定的大鼠品系中均诱发了严重的关节炎。关节炎仅发生在外周关节，这些关节受到了类似于人类疾病中所见的侵蚀性炎症过程的攻击。该疾病具有自限性，宏观上未观察到关节的永久性破坏。疾病的发展似乎依赖于对自体（大鼠）COMP的免疫反应，而不是对其他大鼠软骨胶原蛋白（II型、IX型和XI型）的交叉反应。该疾病以及对COMP的免疫反应受主要组织相容性复合体（MHC）的基因控制；RT1u和RT1l单倍型比a、c、d、f和n单倍型更易患病。LEW和E3基因背景对疾病诱导具有高度易感性。这些发现表明，用大鼠COMP诱导关节炎代表了一种独特的发病机制，与胶原诱导的关节炎或佐剂诱导的关节炎相比，它受不同基因的控制。
