Staging the initiation of autoantibody-induced arthritis: A critical role for immune complexes
Staging the initiation of autoantibody-induced arthritis: A critical role for immune complexes
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DOI：
10.4049/jimmunol.172.12.7694
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Allen, PM
中科院分区：
文献类型：
--
作者：
Wipke, BT;Wang, Z;Allen, PM
在关节炎的K/B X N小鼠模型中，针对葡萄糖-6-磷酸异构酶的自身抗体引起关节特异性炎症和破坏。我们已经使用微型正电子发射断层扫描显示，这些葡萄糖-6-磷酸异构酶特异性自身抗体迅速定位到小鼠的远端关节。在这项研究中，我们使用微正电子发射断层扫描描绘关节炎的发展阶段。抗体的关节定位依赖于肥大细胞，嗜中性粒细胞，和FcRs，但不对C5。令人惊讶的是，抗II型胶原抗体单独没有积累在远端关节，但可以诱导这样做的共同注射无关的预制免疫复合物。对照抗体以类似方式定位于关节。因此，免疫复合物是关节炎的基本引发剂，通过嗜中性粒细胞和肥大细胞的顺序激活，以允许抗体进入关节，在那里它们必须结合靶抗原以引发炎症。我们的研究结果支持了关节炎发展的四阶段模型，并确定了疾病可逆的检查点。
In the K/B X N mouse model of arthritis, autoantibodies against glucose-6-phosphate isomerase cause joint-specific inflammation and destruction. We have shown using micro-positron emission tomography that these glucose-6-phosphate isomerase-specific autoantibodies rapidly localize to distal joints of mice. In this study we used micro-positron emission tomography to delineate the stages involved in the development of arthritis. Localization of Abs to the joints depended upon mast cells, neutrophils, and FcRs, but not on C5. Surprisingly, anti-type II collagen Abs alone did not accumulate in the distal joints, but could be induced to do so by coinjection of irrelevant preformed immune complexes. Control Abs localized to the joint in a similar manner. Thus, immune complexes are essential initiators of arthritis by sequential activation of neutrophils and mast cells to allow Abs access to the joints, where they must bind a target Ag to initiate inflammation. Our findings support a four-stage model for the development of arthritis and identify checkpoints where the disease is reversible.