Division of Rheumatology, Columbia University, College of Physicians & Surgeons, 630 W 168th St, New York, NY 10032 USA.
Arthritis Res Ther. 2012 Feb 24;14(1):R39. doi: 10.1186/ar3752.
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.
本研究旨在探索类风湿关节炎（RA）患者心肌瓜氨酸化的存在和定位，与风湿性和非风湿性疾病对照组进行比较。
收集了 1995 年至 2009 年尸检获得的心肌存档样本，将其分为四组：RA 组；硬皮病组；致死性心肌炎组；非风湿性疾病对照组。由一位心血管病理学家对样本进行免疫组化（IHC）检测，以检测瓜氨酸化和肽基精氨酸脱亚氨酶（PAD）的存在和定位，该病理学家对疾病组和临床特征均不知情。
将十七例 RA 患者的心肌样本与十四例对照组、五例致死性心肌炎患者和十例硬皮病患者的样本进行比较。各组均在心肌间质中检测到强瓜氨酸化染色。然而，与非 RA 组相比，RA 组的平均和峰值抗瓜氨酸化染色分别高出 59%和 44%（两者均 P < 0.05）。各组心肌纤维化程度无差异。与瓜氨酸化不同，PADs 1 至 3 和 6 存在于心肌细胞（主要是 PADs 1 和 3）、固有炎症细胞（主要是 PADs 2 和 4）中，并且在较小程度上存在于内皮细胞和血管平滑肌细胞中。PAD 染色与间质中的抗瓜氨酸化染色不共存，也不因疾病状态而异。
RA 患者心肌间质中瓜氨酸化染色高于其他疾病状态，这一发现可能将自身免疫与 RA 已知的心肌功能障碍和心力衰竭增加联系起来。
