Affiliations: Department of Rheumatology, Faculty of Medical
Sciences, State University of Campinas (UNICAMP), São Paulo,
Brazil | State University of São Paulo, São
Paulo, Brazil
Note: [] Corresponding author: Alzírton de Lira Freire,
Departamento de Clínica Médica, Reumatologia, FCM/UNICAMP, Rua
Alexander Fleming, 40 Campinas, São Paulo, Brazil. CEP: 13083-970, Caixa
Postal: 6111. E-mail: apfreire@hotlink.com.br
Abstract: The aim of this study was to evaluate the frequency and clinical
associations of HLA-DR alleles in Brazilian Caucasian patients with
polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29
Caucasian patients with vasculitis classified as PAN or MPA according to the
American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus
Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for
conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed
using polymerase chain reaction-amplified DNA, hybridized with
sequence-specific low resolution primers. DNA obtained from 59 Caucasian
healthy blood donors were used as control. In order to evaluate if a specific
HLA may have influence on the clinical profile of those diseases, we also
divided the patients according to Birmingham vasculitis score (BVAS) and
Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of
HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in patients with
higher disease activity at the time of diagnosis (BVAS ⩾ 22). Patients with
less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p =
0.011). Patients with gastrointestinal tract involvement had significantly
increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and
B3 (p = 0.008). In contrast, patients with renal disease, had higher frequency
of DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of
patients with MPA, increased frequency of HLA-DRB1*15 was found in patients
with BVAS ⩾ 22 (p = 0.038) and FFS ⩾ 1 (p = 0.039) suggesting that this
allele is associated with more aggressive disease. Antineutrophil cytoplasmic
antibodies (ANCA) negative MPA patients had significantly increased frequency
of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p = 0.023).
Our results suggest that HLA-DR alleles may influence PAN and MPA clinical
expression and outcome and that in MPA they participate in the mechanisms
involved in the development to ANCA.
