ANTI-CYCLIC CITRULLINATED PEPTIDE POSITIVITY IN MYCOBACTERIUM INFECTION IS NON-CITRULLINE DEPENDENT

Background: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) are highly specific for the diagnosis of rheumatoid arthritis. It has been previously shown that a substantial proportion of patients with tuberculosis (TB) are anti-CCP positive(1,2). Objectives: To characterize the citrulline-dependence of the observed anti-CCP positivity in sera of patients with mycobacterium infections Methods: Serum samples of 132 patients with untreated mycobacterium infections (119 TB, 13 atypical mycobacterium) were tested for citrulline-specific reactivity with a first and second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. In 33 patients, a follow-up sample was tested 6 months after starting anti-mycobacterial drugs Results: 132 patients (mean age 51, 69 males/31females) participated in this study. Their origin were diverse (25 born in Israel, 50 in Russia, 39 in Africa and 17 in Asia).Sixty four patients had pulmonary cavitations, 42 bilateral lung infiltrations and 19 suffered from extra-pulmonary tuberculosis. Eight of the patients had concomitant HIV infection, 5 hepatitis B and 8 hepatitis C. Thirty seven had a history of smoking. Twenty-four patients were on corticosteroids. A high percentage of mycobacterium samples turned out to be reactive in a citrulline-independent manner. No difference was noted between TB and atypical mycobacterium samples AntiCCP1/Arginine 1: 14 patients were anti-CCP1 positive, all of them but 1 were anti-arginine positive, 83 patients were anti-arginine positive. Anti-CCP2/Arginine 2: 22 patients were anti-CCP2 positive, all of them but 1 were anti-arginine2 positive, 61 were anti-arginine2 positive. In the subset of 33 patients with a follow-up test 6 months after starting treatment, 1 patient was anti-CCP1 and 4 anti-CCP2 positive at baseline, turning into negative after 6 months. Eighteen of them were anti-arginine 1 positive and 15 anti-arginine 2 positive at baseline, 16 and 12 of them respectively turning into negative after 6 months (the remaining demonstrating a decrease in the titer of antibodies). The presence of anti-CCP/Arginine was found to be significantly correlated with African origin, presence of HIV and treatment with corticosteroids Conclusion: Anti-CCP may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive CCP test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen. References: 1. Elkayam O, Segal R, Lidgi M, Caspi D. Positive anti-cyclic citrullinated proteins and rheumatoid factor during active lung tuberculosis. Ann Rheum Dis. 2006 Aug; 65(8):1110-2. Epub 2005 Dec 16. 2. Kakumanu P, Yamagata H, Sobel ES, Reeves WH, Chan EK, Satoh M. Patients with pulmonary tuberculosis are frequently positive for anti-cyclic citrullinated peptide antibodies, but their sera also react with unmodified arginine-containing peptide. Arthritis Rheum. 2008 Jun;58(6):1576-8 Disclosure of Interest: No disclosureCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 685Session: Infection-related rheumatic diseases (Poster Presentations )