title: HLA-DPB1 as a Risk Factor for Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Cohort Study.
abstract: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) form a group of small-vessel vasculitides with systemic involvement. Although the etiology of AAVs remains largely unknown, both genetic and environmental factors have been implicated. Recently, certain alleles in the HLA-DPB1 region on chromosome 6 were shown to be associated with proteinase 3 (PR3)-ANCA-positive AAV but not with myeloperoxidase (MPO)-ANCA-positive AAV. The aim of this study was to investigate whether different alleles in the HLA-DPB1 region have clinical and/or prognostic implications in AAV.
  
  
  
  One hundred seventy-four patients with a diagnosis of AAV were recruited at the Maastricht University Medical Centre between 2000 and 2009. Seventeen different HLA-DPB1 alleles were determined using the restriction fragment length polymorphism technique. A validation cohort of 170 AAV patients from the Vasculitis Centre of Luebeck/Bad Bramstedt was included.
  
  
  
  In the initial cohort, the distribution of HLA-DPB1 alleles was significantly different between PR3-ANCA-positive compared with MPO-ANCA-positive AAV patients, ANCA-negative AAV patients, and healthy controls. Importantly, HLA-DPB1*04:01 was present in 90% of PR3-ANCA-positive AAV patients compared with 63% of MPO-ANCA-positive AAV patients, 58% of ANCA-negative patients, and 63% of healthy controls. Patients homozygous for HLA-DPB1*04:01 had relapses more often compared with heterozygous patients and noncarrier patients. This association persisted after correction for ANCA subtype and diagnosis. In the validation cohort, patients homozygous for HLA-DPB1*04:01 and those heterozygous for HLA-DPB1*04:01 had relapses more often compared with noncarrier patients. When both patient cohorts were merged (n = 344), homozygous patients relapsed most often, followed by heterozygous patients and noncarrier patients.
  
  
  
  Carriage of HLA-DPB1*04:01 in patients with AAV is significantly associated with an increased risk of relapse compared with HLA-DPB1*04:01-negative patients, irrespective of ANCA status or clinical AAV entity.
authors: Maastricht University, Maastricht, The Netherlands.
authors: Marc
authors: M
authors: Hilhorst
authors: Klinikum Bad Bramstedt, Bad Bramstedt, Germany.
authors: Fabian
authors: F
authors: Arndt
authors: Maastricht University, Maastricht, The Netherlands.
authors: Michael
authors: M
authors: Joseph Kemna
authors: Ruhr University, Bochum, Germany.
authors: Stefan
authors: S
authors: Wieczorek
authors: University Hospital Essen and University Duisburg-Essen, Essen, Germany.
authors: Yoni
authors: Y
authors: Donner
authors: Stanford University, Stanford, California.
authors: Benjamin
authors: B
authors: Wilde
authors: Ruhr University, Bochum, Germany.
authors: Jörg
authors: J
authors: Thomas Epplen
authors: Maastricht University, Maastricht, The Netherlands.
authors: Pieter
authors: P
authors: van Paassen
authors: Maastricht University, Maastricht, The Netherlands.
authors: Jan Willem
authors: JW
authors: Cohen Tervaert
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic; D015331:Cohort Studies; D005260:Female; D059868:HLA-DP beta-Chains / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology; D012008:Recurrence; D012307:Risk Factors
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D053146:Myeloblastin