Cytokines, autoantibodies, and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis - Case-control study nested in a cohort of Norwegian blood donors
- Morten Frisch ( )
- Published Online First 20 July 2007
Objective: To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA).
Methods: Case-control study nested in a prospective cohort of 31,330 blood donors in Oslo, Norway. Forty-nine donors developed RA up to 23 years after their most recent blood donation. Stored sera from these donors (case sera) and a sex- and age-matched sample of 245 healthy donors (control sera), and postdiagnostic sera from 33 of the 49 RA cases, were analyzed for a panel of cytokines and cyto-kine-related markers, autoantibodies and antibodies against Epstein-Barr virus and parvovirus B19.
Results: Cytokines and cytokine-related markers were generally negative in case sera from >5 years before RA diagnosis. In the 5-year interval immediately before RA diagnosis, more case than control sera were positive (odds ratios >2) for interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-10, tumor necrosis factor (TNF) alpha and soluble TNF-receptor I, whereas in postdiagnostic sera, 11 of 16 examined cytokines and cytokine-related markers were statistically significantly elevated compared with control sera. Seropositivity for IgG antibodies against cyclic citrullinated peptides (CCP) and for IgM and IgA rheumatoid factors were seen in case sera from up to 18 years before RA diagnosis. IgG antibodies against Epstein-Barr virus and parvovirus B19 did not differ significantly be-tween case and control sera.
Conclusion: Cytokines and cytokine-related markers appear to be upregulated rather late in RA patho-genesis. In contrast, IgM rheumatoid factor and IgG anti-CCP autoantibodies may precede RA diagno-sis by up to two decades.