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.
The Complexity of Anti-CCP Positive Rheumatoid Arthritis, in the Context of Gene-Environment Associations.
Lundberg, Karin, Bengtsson, Camilla, Israelsson, Lena, Kharlamova, Nastya, Pollak-Dorocic, Iskra, Holmdahl, Rikard, Padyukov, Leonid
Risk factors for rheumatoid arthritis (RA), such as HLA-DRB1'shared epitope' (SE) alleles, PTPN22 and cigarette smoking, associate with anti-CCP positive disease. By subdividing CCP positive patients based on reactivity to CEP-1, the immunodominant B cell epitope on citrullinated alpha-enolase, we have previously shown that SE, PTPN22 and smoking mainly constitute risk factors for CEP-1 positive, rather than CCP positive RA1. In this study, we investigate gene-environment associations with different subsets of RA, based on presence of anti-CCP and specific anti-citrullinated protein/peptide antibodies (ACPAs), including antibodies to CEP-1 and citrullinated peptides from vimentin (Cit-vim), fibrinogen (Cit-fib) and collagen type II (CII Cit-C1).
Presence of antibodies were analysed by ELISA (Immunoscan CCPlus (Euro-Diagnostica) and in-house peptide ELISAs) in 1985 RA patients from the Swedish population-based case-control study EIRA. One hundred and fifty healthy controls were used to determine the 98th percentile cut-off for positivity. A positive and a negative control serum and a standard of pooled antibody-positive sera were included on each plate. Different RA subsets were compared with regard to risk factors, by calculating odds ratios with 95% confidence interval by means of logistic regression.
Antibody frequencies were: CCP (63%); CEP-1 (36%); Cit-vim (37%); Cit-fib (28%); CII Cit-C1 (37%). Most patients showed reactivity to multiple citrullinated antigens, though single-positive subsets of patients were also identified for each specific ACPA. Associations with the risk factors correlated with the number of ACPAs present, as well as anti-CCP antibody levels. However, SE, PTPN22 and smoking associated specifically with CEP-1 positive and Cit-vim positive RA, but not with Cit-fib and Cit-C1 positive RA.
Our data show the complexity of CCP positive RA and that this subset can be further divided based on the fine-specificity of the ACPA response. SE, PTPN22 and smoking seem to predispose for the development of ACPA with multiple reactivities, rather than one single specificity. However, clear differences with regard to gene-environment associations with specific ACPAs can also be identified, suggesting different etiological pathways in different subsets of anti-CCP positive RA patients.
To cite this abstract, please use the following information:
Lundberg, Karin, Bengtsson, Camilla, Israelsson, Lena, Kharlamova, Nastya, Pollak-Dorocic, Iskra, Holmdahl, Rikard, et al; The Complexity of Anti-CCP Positive Rheumatoid Arthritis, in the Context of Gene-Environment Associations. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2161