The genetic control of rheumatoid factor production in a rat model of rheumatoid arthritis
Article first published online: 8 DEC 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 12, pages 3584–3596, December 2003
How to Cite
Wernhoff, P., Olofsson, P. and Holmdahl, R. (2003), The genetic control of rheumatoid factor production in a rat model of rheumatoid arthritis. Arthritis & Rheumatism, 48: 3584–3596. doi: 10.1002/art.11342
- Issue published online: 8 DEC 2003
- Article first published online: 8 DEC 2003
- Manuscript Accepted: 8 AUG 2003
- Manuscript Received: 6 FEB 2003
- Swedish Medical Research Council
- Beijer Foundation
- The Swedish Rheumatism Association
- King Gustaf V's 80-Year Fund
- Anna Greta Crafoord Foundation for Rheumatologic Research
- Kock and Österlund Foundations
- EU projects. Grant Numbers: ERBBIO4CT96056, BMH4-CT97-2522
To investigate the genetic regulation of rheumatoid factor (RF) in a rat model of rheumatoid arthritis, in order to gain understanding of the enigmatic role of RF in the disease.
IgM-RF and IgG-RF, as well as total levels of immunoglobulins of different subclasses, were measured in sera from rats with pristane-induced arthritis (PIA). The major gene regions were identified by linkage analysis of genetically segregating crosses.
The production of RF was found to correlate with development of arthritis and to be higher in females than in males. Surprisingly, the relatively arthritis-resistant E3 strain had higher levels of RF than the arthritis-susceptible DA strain. In an (E3 × DA)F2 cohort a major locus controlling the levels of IgM-RF in serum was identified on chromosome 11 (Rf1) and another on chromosome 16 (Rf3), and these were not related to arthritis susceptibility. However, the Rf2 locus on chromosome 4 controlled IgG-RF levels, IgG2a levels, and chronic arthritis in males (Pia5). Some previously defined arthritis loci (Pia4, Pia6, Pia7, and Pia8) were found to also control immunoglobulin levels in serum.
RFs are produced in the rat PIA model and correlate with development of arthritis. Gene regions controlling RF and serum immunoglobulin levels were identified, of which some cosegregated with arthritis. This suggests a new focus of study to elucidate the role of RF in the pathogenesis of arthritis.