RESEARCH - Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with RA

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Ann Rheum Dis. 2008 Jun;67(6):860-6. Epub 2007 Jul 20.

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.

Jørgensen KT, Wiik A, Pedersen M, Hedegaard CJ, Vestergaard BF,

Gislefoss RE, Kvien TK, Wohlfahrt J, Bendtzen K, Frisch M.

Department of Epidemiology Research, Statens Serum Institut, 5

Artillerivej, DK-2300 Copenhagen, Denmark.

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 analysed for a

panel of cytokines and cytokine-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 the diagnosis of RA. In the 5-year interval

immediately before the diagnosis of RA, more case than control sera

were positive (odds ratios >2) for interleukin (IL)-1 alpha, IL-1

beta, IL-1 receptor antagonist, IL-4, IL-10, tumour necrosis

factor-alpha and soluble tumour necrosis factor receptor I. In

postdiagnostic sera, however, 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 and for IgM and IgA rheumatoid factors

were seen in case sera from up to 18 years before the diagnosis of RA.

IgG antibodies against Epstein-Barr virus and parvovirus B19 did not

differ significantly between case and control sera.

CONCLUSIONS: Cytokines and cytokine-related markers appear to be

upregulated rather late in RA pathogenesis. In contrast, IgM

rheumatoid factor and IgG anti-cyclic citrullinated peptide

autoantibodies may precede the diagnosis of RA by up to two decades.

PMID: 17644543

http://www.ncbi.nlm.nih.gov/pubmed/17644543

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