Dr. Mayes has received consulting fees, speaking fees, and/or honoraria from Actelion, Gilead, United Therapeutics, and MedImmune (less than $10,000 each).
HLA–DRB1*0407 and *1304 are risk factors for scleroderma renal crisis
Version of Record online: 28 JAN 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 2, pages 530–534, February 2011
How to Cite
Nguyen, B., Mayes, M. D., Arnett, F. C., del Junco, D., Reveille, J. D., Gonzalez, E. B., Draeger, H. T., Perry, M., Hendiani, A., Anand, K. K. and Assassi, S. (2011), HLA–DRB1*0407 and *1304 are risk factors for scleroderma renal crisis. Arthritis & Rheumatism, 63: 530–534. doi: 10.1002/art.30111
- Issue online: 28 JAN 2011
- Version of Record online: 28 JAN 2011
- Accepted manuscript online: 27 OCT 2010 02:52PM EST
- Manuscript Accepted: 19 OCT 2010
- Manuscript Received: 10 JUL 2010
- NIH National Center for Research Resources Clinical and Translational Sciences. Grant Number: UL1-RR-024148
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: N01-AR0-2251
- University Clinic Research Center (University of Texas Medical Branch). Grant Number: M01-RR-00073
- University of Texas–San Antonio. Grant Number: M01-RR-01346
- Department of Defense Congressionally Directed Medical Research Programs. Grant Number: PR064251
- National Institute of Arthritis and Musculoskeletal and Skin Diseases Center of Research Translation in Scleroderma. Grant Numbers: P50-AR-054144, KL2-RR-024149-04
To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc).
SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA.
Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti–RNA polymerase III (anti–RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti–RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA–DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27–8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30–15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti–RNAP III, and ACAs, remained significantly associated with SRC in the final model.
The results of this study suggest that DRB1*0407 and *1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.