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. 2013 Jun;72(6):901-7.
doi: 10.1136/annrheumdis-2012-201505. Epub 2012 Aug 21.

Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

Jan M Hughes-Austin  1 , Kevin D Deane, Lezlie A Derber, Jason R Kolfenbach, Gary O Zerbe, Jeremy Sokolove, Lauren J Lahey, Michael H Weisman, Jane H Buckner, Ted R Mikuls, James R O'Dell, Richard M Keating, Peter K Gregersen, William H Robinson, V Michael Holers, Jill M Norris
Affiliations

Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

Jan M Hughes-Austin et al. Ann Rheum Dis. 2013 Jun.

Abstract

Objective: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development.

Methods: We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression.

Results: Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort.

Conclusions: In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.

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Conflict of interest statement

Competing interests A patent application that includes Drs. Deane, Robinson and Holers has been filed for the use of biomarkers to predict clinically actionable events in rheumatoid arthritis. In addition, licensing agreements regarding the use of biomarkers have been established.

Figures

Figure 1
Figure 1
Selection of study population. FDR, firstdegree relatives; HRP, high risk autoantibody profile; RF, rheumatoid factor; SERA, Studies of the Aetiology of Rheumatoid Arthritis.
See this image and copyright information in PMC

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