Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Prognostic and Diagnostic Significance of Autoantibodies to Citrullinated Proteins (ACPA) in Patients with a Scleroderma-Rheumatoid Arthritis (SSc-RA) Overlap Syndrome.
Soejima1, Makoto, Zhijie2, Zhou, Jones1, Donald M., Goudeau1, Danielle, Amity1, Christine L., Frydrych1, Lynne M., Domsic1, Robyn T.
In clinical practice, the anti-CCP test is used to detect ACPA and is used as a diagnostic test for RA. However, approximately 35% of patients with SSc are anti-CCP positive. It is uncertain whether anti-CCP tests are only positive in patients with SSc-RA overlap syndromes or are also positive in patients with SSc only. It is also not clear whether the ACPA antigens recognized by anti-CCP antibodies from anti-CCP positive SSc patients differ from those of RA patients.
We performed a chart review of new sequential patients with a diagnosis of SSc enrolled in a University of Pittsburgh Medical Center (UPMC) SSc registry in the calendar years from 2004 to 2007 (N = 300). We also reviewed the records of 16 other SSc patients seen prior to 2004 who had symptoms suggestive of both SSc and RA. Finally, we reviewed the records of 143 patients from the UPMC RA Comparative Effectiveness Research (RACER) registry. We used the 1987 and 2010 ACR/EULAR RA criteria to determine the number of patients in each group with RA only, with a SSc-RA overlap syndrome or with SSc only. We determined the frequency of interstitial lung disease (ILD) and other clinical features in each group of subjects. Serum samples were analyzed for anti-CCP by ELISA (anti-CCP2; Axis-Shield, UK). A panel of linear and cyclic citrullinated and non-citrullinated peptides derived from fibrinogen, vimentin, enolase and filaggrin were examined by ELISA for reactivity with the same serum samples.
Among the 300 sequential SSc patients seen initially between 2004 and 2007, we identified 8 (2.7%) subjects with RA. The 16 SSc patients seen prior to 2004 also met criteria for a diagnosis of RA. Among the SSc only subjects, 1 was anti-CCP positive and among the SSc-RA overlap subjects, 14 of 24 were anti-CCP positive (p < 0.0001; Fisher's exact test; 99% specificity; 58% sensitivity). 116 of 143 (81%) RA only subjects were anti-CCP positive. Among the anti-CCP positive subjects, the pattern of ACPA peptide reactivity was essentially identical in the SSc-RA overlap subjects as compared to the RA only subjects. There was an increased frequency of ILD, but not other clinical features, among SSc-RA subjects as compared to SSc only subjects (63% vs. 29%, respectively; p=0.0008, Fisher's exact test). Among SSc-RA patients, 63% of anti-CCP positive patients had ILD, while 63% of anti-CCP negative SSc-RA patients had ILD (p=1.0000), suggesting that anti-CCP positivity is not specifically associated with ILD in SSc-RA.
These studies indicate that among patients with SSc, a positive anti-CCP test is highly specific for a SSc-RA overlap syndrome. Furthermore, the ACPA peptide reactivity pattern by ELISA in SSc-RA patients suggests that these patients have RA that is indistinguishable from RA patients without SSc. SSc-RA overlap patients have a higher frequency of ILD suggesting that an overlap of these disorders may promote development of ILD. Taken together, these studies provide a better understanding of the test characteristics of the anti-CCP ELISA and a better understanding of rheumatic overlap syndromes.
To cite this abstract, please use the following information:
Soejima, Makoto, Zhijie, Zhou, Jones, Donald M., Goudeau, Danielle, Amity, Christine L., Frydrych, Lynne M., et al; Prognostic and Diagnostic Significance of Autoantibodies to Citrullinated Proteins (ACPA) in Patients with a Scleroderma-Rheumatoid Arthritis (SSc-RA) Overlap Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :844