Dr. Bernstein has received consulting fees, speaking fees, and/or honoraria from Abbott Canada, Janssen Canada, and Shire Canada (less than $10,000 each); owns stock or stock options in Pfizer; and has served as an expert witness on behalf of Mylan Pharmaceuticals, Barr Pharmaceuticals, Ranbaxy Pharmaceuticals, and Cardinal Health.
Familial clustering of the serum cytokine profile in the relatives of rheumatoid arthritis patients
Article first published online: 25 MAY 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 6, pages 1720–1729, June 2012
How to Cite
El-Gabalawy, H. S., Robinson, D. B., Smolik, I., Hart, D., Elias, B., Wong, K., Peschken, C. A., Hitchon, C. A., Li, X., Bernstein, C. N., Newkirk, M. M. and Fritzler, M. J. (2012), Familial clustering of the serum cytokine profile in the relatives of rheumatoid arthritis patients. Arthritis & Rheumatism, 64: 1720–1729. doi: 10.1002/art.34449
- Issue published online: 25 MAY 2012
- Article first published online: 25 MAY 2012
- Accepted manuscript online: 21 FEB 2012 03:00PM EST
- Manuscript Accepted: 16 FEB 2012
- Manuscript Received: 5 SEP 2011
- Canadian Institutes of Health Research. Grant Numbers: MOP 7770, IIN 84040
Rheumatoid arthritis (RA) is prevalent in North American Native populations, with a high frequency of multicase families and seropositivity in first-degree relatives. This study was undertaken to determine whether the serum cytokine profile of first-degree relatives of North American Native patients with RA differed from that of individuals with no family history of autoimmunity and whether there was an association with RA autoantibodies.
North American Native patients with RA (n = 105), their first-degree relatives (n = 273), healthy North American Native controls (n = 200), and Caucasian controls (n = 150) were studied. Serum levels of 42 cytokines were tested using a multiplex laser bead assay. Rheumatoid factor (RF), anti–cyclic citrullinated peptide 2 (anti–CCP-2), monocyte chemotactic protein 1 (MCP-l), and high-sensitivity C-reactive protein (hsCRP) were tested by enzyme-linked immunosorbent assay, and HLA–DRB1 alleles by specific primers. Discriminant analysis and logistic regression classified individuals based on their cytokine profile.
The prevalence of RF (cutoff level predetermined to include 5% of Caucasian controls) and anti-CCP (cutoff level of ≥40 units) was, respectively, 88% and 81% in the RA patients, 34% and 9% in first-degree relatives, and 9% and 4% in North American Native controls; the prevalence of anti-CCP was 0% in Caucasian controls. Levels of most cytokines were highest in RA patients; 17 of 40 cytokines (43%) were significantly higher in first-degree relatives than in controls, including multiple proinflammatory cytokines. Discriminant analysis showed a notable distinction between the groups, with 85% classification accuracy. First-degree relatives had markedly higher MCP-1 and hsCRP levels than North American Native controls, but there was no consistent association with RA autoantibodies.
Our findings indicate that levels of multiple cytokines and hsCRP are higher in first-degree relatives of North American Native patients with RA compared to individuals from a nonautoimmune background. These data suggest that elevated baseline cytokine levels may be part of the risk profile for developing RA.