Open Access Research article

Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study

Jon T Giles1*, Justyna Fert-Bober2, Jin Kyun Park3, Clifton O Bingham3, Felipe Andrade3, Karen Fox-Talbot4, Dimitrios Pappas1, Antony Rosen3, Jennifer van Eyk2, Joan M Bathon1 and Marc K Halushka4

Author Affiliations

1 Division of Rheumatology, Columbia University, College of Physicians & Surgeons, 630 W 168th St, New York, NY 10032 USA

2 Division of Cardiology, The Johns Hopkins University School of Medicine, The Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA

3 Division of Rheumatology, The Johns Hopkins University School of Medicine, The Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA

4 Department of Pathology, The Johns Hopkins University School of Medicine, The Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA

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Arthritis Research & Therapy 2012, 14:R39  doi:10.1186/ar3752

Published: 24 February 2012

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.