title: HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Texas-Houston.
authors.forename: Binh
authors.initials: B
authors.lastname: Nguyen
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Deborah
authors.initials: D
authors.lastname: del Junco
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.forename: Emilio B
authors.initials: EB
authors.lastname: Gonzalez
authors.forename: Hilda T
authors.initials: HT
authors.lastname: Draeger
authors.forename: Marilyn
authors.initials: M
authors.lastname: Perry
authors.forename: Amir
authors.initials: A
authors.lastname: Hendiani
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Anand
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D000328:Adult; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D012320:RNA Polymerase III / Q000235:genetics / Q000276:immunology; D012042:Registries; D012307:Risk Factors; D045743:Scleroderma, Diffuse / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D013781:Texas / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012320:RNA Polymerase III