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

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.

SUBMITTER: Chang DY

PROVIDER: S-EPMC3408128 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Chang Dong-yuan DY Luo Huan H Zhou Xu-jie XJ Chen Min M Zhao Ming-Hui MH

Clinical journal of the American Society of Nephrology : CJASN 20120517 8

<h4>Background and objectives</h4>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).<h4>Design, setting, participants, & measurements</h4>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 anal ...[more]

PMID: 22595829

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Project description:Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.

Dataset Information

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

Publications

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

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