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本文引用的文献

1
Diagnosis and risk stratification in patients with anti-RNP autoimmunity.抗RNP自身免疫患者的诊断与风险分层
Lupus. 2015 Sep;24(10):1057-66. doi: 10.1177/0961203315575586. Epub 2015 Mar 2.
2
Conservation of pathogenic TCR homology across class II restrictions in anti-ribonucleoprotein autoimmunity: extended efficacy of T cell vaccine therapy.抗核糖核蛋白自身免疫中 II 类限制的致病性 TCR 同源性的保守性：T 细胞疫苗治疗的疗效扩展。
J Immunol. 2014 May 1;192(9):4093-102. doi: 10.4049/jimmunol.1203197. Epub 2014 Mar 26.
3
Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthritis-associated interstitial lung disease.鉴定瓜氨酸化热休克蛋白90异构体作为类风湿关节炎相关间质性肺病中的新型自身抗原。
Arthritis Rheum. 2013 Apr;65(4):869-79. doi: 10.1002/art.37881.
4
Distinct phenotypes in mixed connective tissue disease: subgroups and survival.混合性结缔组织病的不同表型：亚组与生存。
Lupus. 2012 Nov;21(13):1412-22. doi: 10.1177/0961203312456751. Epub 2012 Aug 3.
5
Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?中性粒细胞依赖性白细胞介素 6 转导信号介导的内皮细胞激活和凋亡：系统性硬化症的新靶点？
Ann Rheum Dis. 2011 Feb;70(2):366-72. doi: 10.1136/ard.2010.133587. Epub 2010 Nov 10.
6
Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions.硬皮病的指端溃疡：通过观察 1614 个指端病变进行分期、特征分析和亚组划分。
Rheumatology (Oxford). 2010 Jul;49(7):1374-82. doi: 10.1093/rheumatology/keq097. Epub 2010 Apr 16.
7
[Severe corticoid-refractory autoimmune thrombocytopenia associated with mixed connective tissue disease (Sharp's syndrome). Treatment with rituximab].[与混合性结缔组织病（夏普综合征）相关的严重皮质类固醇难治性自身免疫性血小板减少症。利妥昔单抗治疗]
Dtsch Med Wochenschr. 2009 Sep;134(36):1734-8. doi: 10.1055/s-0029-1234008. Epub 2009 Aug 28.
8
MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial.新型硝酸甘油制剂MQX-503改善雷诺现象严重程度：一项随机对照试验
Arthritis Rheum. 2009 Mar;60(3):870-7. doi: 10.1002/art.24351.
9
Tissue targeting of anti-RNP autoimmunity: effects of T cells and myeloid dendritic cells in a murine model.抗核糖核蛋白自身免疫的组织靶向性：小鼠模型中T细胞和髓样树突状细胞的作用
Arthritis Rheum. 2009 Feb;60(2):534-42. doi: 10.1002/art.24256.
10
Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.FOXO3a和Akt对Bim的转录调控介导了硬皮病血清诱导的内皮祖细胞凋亡。
Circulation. 2008 Nov 18;118(21):2156-65. doi: 10.1161/CIRCULATIONAHA.108.787200. Epub 2008 Nov 3.

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.

DOI:10.1002/art.40505
PMID:29569858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6115278/
Abstract

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.

摘要

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。