EXTENDED REPORT

Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset

E Berglin¹, T Johansson², U Sundin⁶, E Jidell³, G Wadell⁴, G Hallmans⁵, S Rantapää-Dahlqvist¹

¹ Department of Rheumatology, University Hospital, Umeå, Sweden
² Department of Medical Biochemistry and Biophysics/Omnio, University Hospital, Umeå
³ Department of Transfusion Medicine, University Hospital, Umeå
⁴ Department of Virology, University Hospital, Umeå
⁵ Department of Nutritional Research, University Hospital, Umeå
⁶ Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden

Correspondence to:
Dr Solbritt Rantapää-Dahlqvist
Department of Public Health and Clinical Medicine, Rheumatology, University Hospital, 901 85 Umeå, Sweden; solbritt.rantapaa.dahlqvist{at}medicin.umu.se

Objective: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression.

Methods: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified.

Results: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis.

Conclusions: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.

Abbreviations: ACR, American College of Rheumatology; anti-CCP, antibodies against cyclic citrullinated peptide; DAS28, 28 joint disease activity score; DMARD, disease modifying antirheumatic drug; EULAR, European League Against Rheumatism; NSHDS, Northern Sweden Health and Disease Study; RF, rheumatoid factor; SE, shared epitope

Keywords: anti-CCP antibody; rheumatoid factors; early rheumatoid arthritis; radiological outcome; titre of anti-CCP antibodies

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Song, Y.W., Kang, E.H. (2009). Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM 0: hcp165v1-hcp165 [Abstract] [Full Text]  
• RENESES, S., GONZALEZ-ESCRIBANO, M. F., FERNANDEZ-SUAREZ, A., PESTANA, L., DAVILA, B., WICHMANN, I., GARCIA, A. (2009). The Value of HLA-DRB1 Shared Epitope, -308 Tumor Necrosis Factor-{alpha} Gene Promoter Polymorphism, Rheumatoid Factor, Anti-Citrullinated Peptide Antibodies, and Early Erosions for Predicting Radiological Outcome in Recent-Onset Rheumatoid Arthritis. The Journal of Rheumatology 36: 1143-1149 [Abstract] [Full Text]  
• Hoppe, B, Haupl, T, Egerer, K, Gruber, R, Kiesewetter, H, Salama, A, Burmester, G R, Dorner, T (2009). Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis. Ann Rheum Dis 68: 898-903 [Abstract] [Full Text]  
• Teng, Y K O, Levarht, E W N, Toes, R. E M, Huizinga, T. W J, van Laar, J. M (2009). Residual inflammation after rituximab treatment is associated with sustained synovial plasma cell infiltration and enhanced B cell repopulation. Ann Rheum Dis 68: 1011-1016 [Abstract] [Full Text]  
• Hetland, M L, Ejbjerg, B, Horslev-Petersen, K, Jacobsen, S, Vestergaard, A, Jurik, A G, Stengaard-Pedersen, K, Junker, P, Lottenburger, T, Hansen, I, Andersen, L S, Tarp, U, Skjodt, H, Pedersen, J K, Majgaard, O, Svendsen, A J, Ellingsen, T, Lindegaard, H, Christensen, A F, Vallo, J, Torfing, T, Narvestad, E, Thomsen, H S, Ostergaard, M, and the CIMESTRA study group, (2009). MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Ann Rheum Dis 68: 384-390 [Abstract] [Full Text]  
• Lee, D M, Phillips, R, Hagan, E M, Chibnik, L B, Costenbader, K H, Schur, P H (2009). Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association with tobacco exposure in patients with rheumatoid arthritis. Ann Rheum Dis 68: 201-208 [Abstract] [Full Text]  
• IWAMOTO, N., KAWAKAMI, A., TAMAI, M., FUJIKAWA, K., ARIMA, K., ARAMAKI, T., KAWASHIRI, S., ICHINOSE, K., KAMACHI, M., NAKAMURA, H., ORIGUCHI, T., IDA, H., EGUCHI, K. (2009). Determination of the Subset of Sjogren's Syndrome with Articular Manifestations by Anticyclic Citrullinated Peptide Antibodies. The Journal of Rheumatology 36: 113-115 [Abstract] [Full Text]  
• Liao, K P, Batra, K L, Chibnik, L, Schur, P H, Costenbader, K H (2008). Anti-cyclic citrullinated peptide revised criteria for the classification of rheumatoid arthritis. Ann Rheum Dis 67: 1557-1561 [Abstract] [Full Text]  
• Visser, K, Verpoort, K N, van Dongen, H, van der Kooij, S M, Allaart, C F, Toes, R E M, Huizinga, T W J, van der Helm-van Mil, A H M (2008). Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are associated with the response to methotrexate in recent-onset arthritis. Ann Rheum Dis 67: 1194-1195 [Full Text]  
• Majka, D S, Deane, K D, Parrish, L A, Lazar, A A, Baron, A E, Walker, C W, Rubertone, M V, Gilliland, W R, Norris, J M, Holers, V M (2008). Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis. Ann Rheum Dis 67: 801-807 [Abstract] [Full Text]  
• Nishimoto, K, Ikari, K, Mochizuki, T, Tomatsu, T, Toyama, Y, Hara, M, Yamanaka, H, Kamatani, N, Momohara, S (2008). Lack of association between PADI4 and functional severity in Japanese rheumatoid arthritis patients. Ann Rheum Dis 67: 431-432 [Full Text]  
• Syversen, S W, Gaarder, P I, Goll, G L, Odegard, S, Haavardsholm, E A, Mowinckel, P, van der Heijde, D, Landewe, R, Kvien, T K (2008). High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 67: 212-217 [Abstract] [Full Text]  
• Naseem, H, Thomson, W, Silman, A, Worthington, J, Symmons, D, Barton, A (2008). The PTPN22*C1858T functional polymorphism is associated with susceptibility to inflammatory polyarthritis but neither this nor other variants spanning the gene is associated with disease outcome. Ann Rheum Dis 67: 251-255 [Abstract] [Full Text]  
• Lie, B. A, Viken, M. K, Odegard, S., van der Heijde, D., Landewe, R., Uhlig, T., Kvien, T. K (2007). Associations between the PTPN22 1858C->T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 66: 1604-1609 [Abstract] [Full Text]  
• Linn-Rasker, S P, van der Helm-van Mil, A H M, Breedveld, F C, Huizinga, T W J (2007). Arthritis of the large joints--in particular, the knee--at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis. Ann Rheum Dis 66: 646-650 [Abstract] [Full Text]  
• Bobbio-Pallavicini, F., Caporali, R., Alpini, C., Avalle, S., Epis, O. M, Klersy, C., Montecucco, C. (2007). High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor {alpha} inhibitors in rheumatoid arthritis. Ann Rheum Dis 66: 302-307 [Abstract] [Full Text]  
• Rantapaa-Dahlqvist, S, Boman, K, Tarkowski, A, Hallmans, G (2007). Up regulation of monocyte chemoattractant protein-1 expression in anti-citrulline antibody and immunoglobulin M rheumatoid factor positive subjects precedes onset of inflammatory response and development of overt rheumatoid arthritis. Ann Rheum Dis 66: 121-123 [Abstract] [Full Text]  
• Salmon, J. E., Paget, S. A., Roman, M. J. (2006). Carotid Atherosclerosis and Rheumatoid Arthritis.. ANN INTERN MED 145: 231-231 [Full Text]