ASSOCIATIONS OF EROSIVE ARTHRITIS WITH ANTI-CCP ANTIBODIES AND MHC CLASS II ALLELES IN SLE

Background: Synovitis is a clinical feature of SLE, with 5% of patients developing erosive arthritis (EA) [1]. Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been detected in RA, psoriatic arthritis (PsA), and SLE [1–3]. In both RA and PsA, anti-CCP antibodies are associated with EA and the shared epitope (SE) [3,4].Objectives: We investigated SLE patients for the associations of EA with anti-CCP and MHC Class II alleles.Methods: We studied 104 patients (91 females, 13 males) who fulfilled the ACR 1997 revised criteria for SLE. Patients' records were reviewed and radiographs of hands and feet were studied for joint erosions. Blood samples were obtained for serological and genetic testing. We used 130 age and sex-matched blood donors as serological controls and 244 blood donors as genetic controls. Serum autoantibodies were assayed using commercial ELISA kits (anti-CCP2, IgM RF: INOVA, USA; anti-U1RNP: Binding Site, UK). HLA-DRB1 and DQB1 typing were performed by polymerase chain reaction using sequence specific primers (PCR-SSP). Statistical associations were tested using odds ratios (OR) with 95% confidence intervals (CI), and Chi square tests, with Fisher's tests where appropriate.Results: Eleven patients (11%) developed EA. Anti-CCP positivity was more frequent among SLE patients (8/104, 8%) than in controls (2/130, 1.5%),(OR=5.3, 95%CI:1.1-25.7,p=0.02), and more so among patients with synovitis (8/71, 11%). Four of the eight anti-CCP positive patients (50%), all of whom had synovitis, developed EA (OR=12.7, 95%CI:2.6-62.5,p=0.004). RF and anti-U1-RNP were not associated with EA. HLA-DQB1*0302 was associated with both EA (OR=11.1, 95%CI:2.7-46.1,p=0.001) and anti-CCP (OR=5.9, 95%CI:1.3-27.0,p=0.02). HLA-DRB1*0401 was associated with EA (OR=4.7, 95%CI:1.3-17.0,p=0.02), but not with anti-CCP. Two SE copies were associated with EA (OR=10.8, 95%CI:2.2-54.4,p=0.005), with a trend towards an association with anti-CCP (OR=5.2, 95%CI:0.9-29.5,p=0.08).Conclusion: Anti-CCP positive SLE patients are at increased risk of developing EA, particularly if they present with synovitis. The associations of HLA-DRB1*0401 and HLA-DQB1*0302 with EA support the influence of MHC Class II alleles on the development of EA. Our results suggest that anti-CCP may be a useful serological marker for EA in SLE.References: 1. Mediwake R, et al. Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 60(1):67-68.2. Schellekens GA, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155-163.3. Korendowych E, et al. The clinical and genetic associations of anti-cyclic citrullinated peptide antibodies in psoriatic arthritis. Rheumatology 44(8):1056-1060.4. Wagner U, et al. HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. Arthritis Rheum 40(2):341-351.Citation: Ann Rheum Dis, volume 66, supplement II, year 2007, page 86Session: Undifferentiated connective tissue diseases and overlap syndromes