Relationship among the HLA–DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis
Article first published online: 12 AUG 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis Care & Research
Volume 47, Issue 4, pages 403–407, 15 August 2002
How to Cite
Mattey, D. L., Dawes, P. T., Clarke, S., Fisher, J., Brownfield, A., Thomson, W., Haajeer, A. H. and Ollier, W. E. R. (2002), Relationship among the HLA–DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis. Arthritis & Rheumatism, 47: 403–407. doi: 10.1002/art.10514
- Issue published online: 12 AUG 2002
- Article first published online: 12 AUG 2002
- Manuscript Accepted: 18 JAN 2002
- Manuscript Received: 10 NOV 2001
- Arthritis Research Campaign
- Haywood Rheumatism Research and Development Foundation
- European Commission. Grant Number: BMH4-CT-0396
- Rheumatoid arthritis;
- Rheumatoid factor;
- Shared epitope
Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA–DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE.
The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA–DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis.
Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking.
Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA–DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA–DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.