HLA–DPB1 as a Risk Factor for Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: A Cohort Study

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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.

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