Rheumatology Advance Access originally published online on June 16, 2006
Rheumatology 2007 46(1):70-75; doi:10.1093/rheumatology/kel202
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Citrullination in extra-articular manifestations of rheumatoid arthritis
1Mayo Clinic College of Medicine, Rochester, MN, USA, 2Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, The Netherlands, 3Department of Internal Medicine I, University of Regensburg, Germany and 4Department of Rheumatology, Malmö University Hospital, Sweden
Correspondence to: Tim Bongartz, MD, Division of Rheumatology, Mayo Clinic College of Medicine, 200 1St St SW Rochester, MN 55905, USA. E-mail: Bongartz.tim{at}mayo.edu
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Abstract |
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Background. Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules.
Methods. Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed.
Results. Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use.
Rheumatoid nodules were citrulline positive in a majority of cases (70%).
Conclusion. Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.
KEY WORDS: Citrullination, Interstitial pneumonia, Rheumatoid arthritis, Extra-articular disease, Rheumatoid nodules