Association of HLA genes with clinical outcomes of ANCA-associated vasculitis

Clin J Am Soc Nephrol. 2012 Aug;7(8):1293-9. doi: 10.2215/CJN.13071211. Epub 2012 May 17.

Abstract

Background and objectives: The HLA system plays a central role in the distinction between self antigens and non-self antigens. This study aimed to investigate the association between HLA genes and the outcomes of patients with ANCA-associated vasculitis (AAV).

Design, setting, participants, & measurements: This study recruited 152 consecutive Chinese patients with AAV. The predictive value of the HLA alleles for renal outcome, response to treatment, and all-cause mortality were analyzed.

Results: The proportion of patients with treatment failure was significantly higher in DRB1*0405-positive patients than in DRB1*0405-negative patients (41.7% versus 12.9%; P=0.008; corrected P=0.02). After adjusting for the other potential predictors, DRB1*0405 was still an independent predictor for the poor response to treatment (hazard ratio [HR], 5.91; 95% confidence interval [95% CI], 1.23-28.52; P=0.03). Renal survival was significantly worse in patients with DRB1*0405 than those without DRB1*0405 (P<0.001; corrected P<0.001). After adjusting for the other potential predictors, DRB1*0405 was still an independent predictor for ESRD (HR, 5.50; 95% CI, 2.18-13.88; P<0.001). The probability of all-cause mortality in patients with DPB1*0402 was significantly higher than those without DPB1*0402 (P=0.02; corrected P=0.04). After adjusting for the other potential predictors, DPB1*0402 was still an independent predictor for all-cause mortality (HR, 2.52; 95% CI, 1.21-5.28; P=0.01).

Conclusions: In AAV patients, DRB1*0405 might be an independent risk factor for the poor response to treatment and the deterioration of renal function, whereas DPB1*0402 might be an independent risk factor for all-cause mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / genetics*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / mortality
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / physiopathology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / therapy
  • Chi-Square Distribution
  • China
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-DP beta-Chains / genetics
  • HLA-DR1 Antigen / genetics*
  • HLA-DRB1 Chains / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney / physiopathology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Plasma Exchange
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Failure
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • HLA-DP beta-Chains
  • HLA-DPB1*04:02 antigen
  • HLA-DR1 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*04:05 antigen
  • Immunosuppressive Agents