TY - JOUR
T1 - Myocardial citrullination in rheumatoid arthritis
T2 - A correlative histopathologic study
AU - Giles, Jon T.
AU - Fert-Bober, Justyna
AU - Park, Jin K.
AU - Bingham, Clifton O.
AU - Andrade, Felipe
AU - Fox-Talbot, Karen
AU - Pappas, Dimitrios
AU - Rosen, Antony
AU - van Eyk, Jennifer
AU - Bathon, Joan M.
AU - Halushka, Marc K.
N1 - Funding Information:
Funding for this research was made possible by grants from the ACR Research and Education Foundation ‘Within Our Reach: Finding a Cure for Rheumatoid Arthritis’ campaign (JTG and COB) and by a grant from the Donald B and Dorothy L Stabler Foundation. The funding sources exerted no control over the final content of this manuscript.
PY - 2012/2/24
Y1 - 2012/2/24
N2 - 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.
AB - 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.
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U2 - 10.1186/ar3752
DO - 10.1186/ar3752
M3 - Article
C2 - 22364592
AN - SCOPUS:84862778953
SN - 1478-6354
VL - 14
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - R39
ER -