雷诺现象的自身免疫基础：鼠模型与人类疾病。
An Autoimmune Basis for Raynaud's Phenomenon: Murine Model and Human Disease.
机构信息
Miami VA Medical Center and University of Miami Miller School of Medicine, Miami, Florida.
University of Miami Miller School of Medicine, Miami, Florida.
出版信息
Arthritis Rheumatol. 2018 Sep;70(9):1489-1499. doi: 10.1002/art.40505. Epub 2018 Jul 25.
OBJECTIVE
Raynaud's phenomenon (RP) is common in anti-RNP-positive patients with rheumatic diseases but is not itself known to be caused by autoimmunity. The aim of this study was to assess autoantibodies that could mediate this process.
METHODS
Antibodies derived from patient sera and from murine models of anti-RNP autoimmunity were screened for the ability to induce RP-like tissue ischemia and endothelial cell apoptosis in murine models and in vitro systems.
RESULTS
RNP-positive sera from RP patients and murine sera from RNP-positive B cell adoptive transfer recipients induced RP-like tissue ischemia and endothelial cell apoptosis. Proteomic analysis identified cytokeratin 10 (K10) as a candidate autoantigen in RP. Monoclonal anti-K10 antibodies reproduced patterns of ischemic tissue loss and endothelial cell apoptosis; K10 knockout or depletion of anti-K10 activity in serum was protective. Cold exposure enhanced K10 expression and in vivo tissue loss.
CONCLUSION
Anti-K10 antibodies are sufficient to mediate RP-like ischemia in murine models and are implicated in the pathogenesis of RP in patients with anti-RNP autoimmunity.
目的
雷诺现象（RP）在抗 RNP 阳性的风湿性疾病患者中很常见，但自身免疫并不是其发病原因。本研究旨在评估可能介导这一过程的自身抗体。
方法
从患者血清和抗 RNP 自身免疫的鼠模型中提取的抗体，在鼠模型和体外系统中筛选其诱导 RP 样组织缺血和内皮细胞凋亡的能力。
结果
RP 患者的 RNP 阳性血清和 RNP 阳性 B 细胞过继转移受者的鼠血清诱导 RP 样组织缺血和内皮细胞凋亡。蛋白质组学分析鉴定角蛋白 10（K10）为 RP 的候选自身抗原。单克隆抗 K10 抗体重现缺血组织丢失和内皮细胞凋亡的模式；K10 敲除或血清中抗 K10 活性耗竭具有保护作用。冷暴露增强了 K10 的表达，导致体内组织丢失。
结论
抗 K10 抗体足以介导鼠模型中的 RP 样缺血，并且与抗 RNP 自身免疫患者的 RP 发病机制有关。
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