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Arthritis Rheum. 2010 Nov;62(11):3161-72. doi: 10.1002/art.27638.

The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner.

Author information

  • 1Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Kevin.Deane@UCDenver.edu

Abstract

OBJECTIVE:

To evaluate levels of biomarkers in preclinical rheumatoid arthritis (RA) and to use elevated biomarkers to develop a model for the prediction of time to future diagnosis of seropositive RA.

METHODS:

Stored samples obtained from 73 military cases with seropositive RA prior to RA diagnosis and from controls (mean 2.9 samples per case; samples collected a mean of 6.6 years prior to diagnosis) were tested for rheumatoid factor (RF) isotypes, anti-cyclic citrullinated peptide (anti-CCP) antibodies, 14 cytokines and chemokines (by bead-based assay), and C-reactive protein (CRP).

RESULTS:

Preclinical positivity for anti-CCP and/or ≥2 RF isotypes was >96% specific for future RA. In preclinical RA, levels of the following were positive in a significantly greater proportion of RA cases versus controls: interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, fibroblast growth factor 2, flt-3 ligand, tumor necrosis factor α, interferon-γ-inducible 10-kd protein, granulocyte-macrophage colony-stimulating factor, and CRP. Also, increasing numbers of elevated cytokines/chemokines were present in cases nearer to the time of diagnosis. RA patients who were ≥40 years old at diagnosis had a higher proportion of samples positive for cytokines/chemokines 5-10 years prior to diagnosis than did patients who were <40 years old at diagnosis (P < 0.01). In regression modeling using only case samples positive for autoantibodies highly specific for future RA, increasing numbers of cytokines/chemokines were predictive of decreased time to diagnosis, and the predicted time to diagnosis based on cytokines/chemokines was longer in older compared with younger cases.

CONCLUSION:

Levels of autoantibodies, cytokines/chemokines, and CRP are elevated in the preclinical period of RA development. In preclinical autoantibody-positive cases, the number of elevated cytokines/chemokines is predictive of the time of diagnosis of future RA in an age-dependent manner.

Copyright © 2010 by the American College of Rheumatology.

PMID:
20597112
[PubMed - indexed for MEDLINE]
PMCID:
PMC2980824
Free PMC Article

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