Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Antibodies of IgG, IgA and IgM Isotypes Against Cyclic Citrullinated Peptide Precede the Development of Rheumatoid Arthritis.

Kokkonen2,  Heidi, Mullazehi4,  Mohammed, Berglin2,  Ewa, Hallmans1,  Göran, Wadell3,  Göran, Ronnelid4,  Johan, Rantapaa-Dahlqvist2,  Solbritt

Department of Nutritional Research, Umeå University, Umeå
Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå
Department of Virology, Umeå University, Umeå
Division of Clinical Immunology, Uppsala University, Uppsala

Background and Statement of Purpose:

We have previously shown that the presence of anti-cyclic citrullinated peptide (CCP) antibodies precedes the development of rheumatoid arthritis (RA) by several years. In a recent study we also showed that individuals who later developed RA had significantly increased levels of several cytokines, cytokine-related factors, and chemokines. In this study we aimed firstly to investigate the presence and predictive value of isotypes, IgG, IgA and IgM, of anti-CCP antibodies in individuals before onset of symptoms of RA and to assess their relation to rheumatoid factors (RF), cytokines and chemokines, genetic factors, and smoking habits, and secondly to evaluate the predictive effect of these predating antibodies for radiological score after disease onset.

Methods:

A case-control study was nested within the Medical Biobank and the Maternity cohorts of Northern Sweden. Patients with RA were identified amongst blood donors antedating onset of their disease by years by co-analyzing the registers of the patients and for the biobanks. Controls, matched for age, sex, date of sampling and residential area, were selected randomly from the same cohorts. Anti-CCP antibody isotypes were determined using EliA anti-CCP assay on ImmunoCAP 250 (Phadia AB, Uppsala, Sweden)

Results:

Eighty-six individuals with RA were identified as being blood donors prior to onset of symptoms of joint disease, median (IQR), 2.5 (1.1–5.9) years before onset, with 71 available samples. The prevalence of anti-CCP antibodies in the pre-patient samples was 35.2% of IgG, 23.9% of IgA, and 11.8% of IgM with a specificity of 98.9%, 97.1% and 93.9%, respectively. IgG- and IgA anti-CCP antibodies were highly significant compared with controls, whereas the IgM isotype did not reach statistical significance compared with controls. Anti-CCP antibody of the IgG and IgA isotype predicted RA significantly in conditional logistic regression models (OR=98.1, 95% CI (13.3–723.8) and OR=13.3, 95% CI (4.9–36.0), respectively), whereas the IgM isotype showed borderline significance (OR=2.5 95% CI (0.9–6.3)). The mean antedating time was longest for IgA isotype, 2.2 years, followed by IgG, 2.1 years and for IgM, shortest, 1.4 years. The concentrations of the antibodies increased significantly and the frequencies of the isotypes increased significantly until disease onset and where at diagnosis of RA 70%, 40% and 30%, respectively. IgA antibodies but not IgG were significantly associated with up-regulated chemokines. In smokers IgA anti-CCP antibodies appeared much earlier before onset of symptoms of RA vs. in non-smokers. Patients positive for all three anti-CCP antibody isotypes already before onset of symptoms had a higher radiographic score both at baseline and after 24 months of disease compared with pre-RA individuals with fewer or no anti-CCP2 isotypes before onset.

Conclusions:

Anti-CCP antibodies of both the IgG and IgA isotypes pre-dated the onset of RA by several years, also, anti-CCP antibodies of both IgG and IgA isotypes predicted the development of RA, with the highest predictive value for IgG antibodies.

To cite this abstract, please use the following information:
Kokkonen, Heidi, Mullazehi, Mohammed, Berglin, Ewa, Hallmans, Göran, Wadell, Göran, Ronnelid, Johan, et al; Antibodies of IgG, IgA and IgM Isotypes Against Cyclic Citrullinated Peptide Precede the Development of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2115
DOI: 10.1002/art.29879

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