Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study.

Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study.
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DOI:
10.1186/ar3752
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发表时间:
2012-02-24
影响因子:
4.9
通讯作者:
Halushka MK
Halushka MK
中科院分区:
医学2区
文献类型:
--
作者:
Giles JT;Fert-Bober J;Park JK;Bingham CO 3rd;Andrade F;Fox-Talbot K;Pappas D;Rosen A;van Eyk J;Bathon JM;Halushka MK

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本研究的目的是与风湿性和非风湿性疾病对照组比较,探讨类风湿关节炎(RA)患者样本中心肌瓜氨酸化的存在和定位。从1995年到2009年尸检期间获得的存档心肌样本被组合成四组:RA、硬皮病、致死性心肌炎和非风湿性疾病对照组。采用免疫组织化学方法(IHC),由一位对疾病组和临床特征视而不见的心血管病理学家检查瓜氨酸化和肽基精氨酸脱亚胺酶(PADS)的存在和定位。17例RA患者的心肌样本与14名对照组、5名致死性心肌炎患者和10名硬皮病患者的心肌样本进行了比较。每组大鼠心肌间质均可检测到较强的瓜氨酸化染色。然而,类风湿性关节炎组的抗瓜氨酸染色的平均值和峰值分别比非类风湿性关节炎联合组高59%和44%(两组比较P<0.05)。心肌纤维化在两组之间没有不同。与瓜氨酸化相反,PAD1至PAD3和PAD6在心肌细胞(主要是PAD1和3)、常驻炎症细胞(主要是PAD2和4)中检测到,少量在内皮细胞和血管平滑肌细胞中检测到。PAD染色与抗瓜氨酸染色在间质中不共定位,且不随病情变化而变化。与其他疾病状态相比,RA心肌间质的瓜氨酸化染色较高,这一发现可能将自身免疫与RA心肌功能障碍和心力衰竭的已知增加联系起来。
The aim of this study was to explore the presence and localization of myocardial citrullination in samples from rheumatoid arthritis (RA) patients compared to rheumatic and non-rheumatic disease control groups. Archived myocardial samples obtained during autopsy from 1995 to 2009 were assembled into four groups: RA; scleroderma; fatal myocarditis; and non-rheumatic disease controls. Samples were examined by immunohistochemistry (IHC) for the presence and localization of citrullination and peptidyl arginine deiminase enzymes (PADs) by a single cardiovascular pathologist blinded to disease group and clinical characteristics. Myocardial samples from seventeen RA patients were compared with those from fourteen controls, five fatal myocarditis patients, and ten scleroderma patients. Strong citrullination staining was detected exclusively in the myocardial interstitium in each of the groups. However, average and peak anti-citrulline staining was 59% and 44% higher, respectively, for the RA group compared to the combined non-RA groups (P < 0.05 for both comparisons). Myocardial fibrosis did not differ between the groups. In contrast to citrullination, PADs 1 to 3 and 6 were detected in cardiomyocytes (primarily PADs 1 and 3), resident inflammatory cells (primarily PADs 2 and 4), and, to a smaller extent, in endothelial cells and vascular smooth muscle cells. PAD staining did not co-localize with anti-citrulline staining in the interstitium and did not vary by disease state. Staining for citrullination was higher in the myocardial interstitium of RA compared to other disease states, a finding that could link autoimmunity to the known increase in myocardial dysfunction and heart failure in RA.
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