KRN/I-Ag7 关节炎与补体 C3 无关。
KRN/I-Ag7 mouse arthritis is independent of complement C3.
机构信息
Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
出版信息
J Clin Immunol. 2011 Oct;31(5):857-63. doi: 10.1007/s10875-011-9562-2. Epub 2011 Jul 6.
BACKGROUND
KRN/I-A(g7) (KxB/N) is a mouse model of inflammatory arthritis, which resembles human rheumatoid arthritis. Arthritis in these animals is caused by autoreactivity to a ubiquitously expressed autoantigen, glucose-6 phosphate isomerase. Tolerance is broken at both the T cell and B cell level. The sera from KRN/I-A(g7) mice can induce mouse arthritis in healthy mice. Complement components of the alternative complement pathway, including C3, have been shown to be required in induction of mouse arthritis by serum transfer.
METHODS
We have bred KRN/I-A(g7) mice onto a C3-deficient background and followed cohorts for the spontaneous appearance of arthritis. We have also transferred KxB/N serum to B6.I-A ( g7 ) recipients.
RESULTS
C3-deficient KRN/I-A(g7) mice spontaneously developed severe, destructive arthritis, comparable to that seen in C3-intact KRN/I-A(g7) mice. However, serum transfer experiments confirmed the strong requirement for C3 in the passive model.
CONCLUSION
The pathogenesis of spontaneous KRN/I-A(g7) arthritis can largely proceed by complement-independent pathways and must have pathology effector mechanisms in addition to those seen in the passive serum transfer model.
背景
KRN/I-A(g7)（KxB/N）是一种炎症性关节炎的小鼠模型，类似于人类类风湿关节炎。这些动物的关节炎是由对广泛表达的自身抗原葡萄糖-6-磷酸异构酶的自身反应引起的。在 T 细胞和 B 细胞水平都存在耐受破坏。KRN/I-A(g7) 小鼠的血清可在健康小鼠中诱导出关节炎。补体替代途径的补体成分，包括 C3，已被证明在血清转移诱导小鼠关节炎中是必需的。
方法
我们将 KRN/I-A(g7) 小鼠繁殖到 C3 缺陷背景上，并对其进行自发性关节炎出现的队列研究。我们还将 KxB/N 血清转移到 B6.I-A(g7) 受体中。
结果
C3 缺陷的 KRN/I-A(g7) 小鼠自发地发生严重的、破坏性关节炎，与 C3 完整的 KRN/I-A(g7) 小鼠中所见的关节炎相当。然而，血清转移实验证实了 C3 在被动模型中强烈的需求。
结论
自发性 KRN/I-A(g7) 关节炎的发病机制可以很大程度上通过补体非依赖性途径进行，并且除了在被动血清转移模型中所见的机制之外，还必须有病理效应机制。
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