HLA-DR4, DR13(6) and the ancestral haplotype A1B8DR3 are associated with ANCA-associated vasculitis and Wegener's granulomatosis

Rheumatology (Oxford). 2009 Jun;48(6):622-5. doi: 10.1093/rheumatology/kep057. Epub 2009 Mar 31.

Abstract

Objectives: As the HLA system is involved in recognition of self and non-self, an association with the development of ANCA-associated vasculitis (AAV) seems probable. In this study, the relation between HLA antigens and AAV and it's severity were investigated.

Methods: Consecutive patients diagnosed with AAV at our centre, who were followed for at least 2 years, were included. The frequency of HLA antigens of AAV and WG patients was compared with 5872 healthy blood donors from the same region and with 4000 healthy Dutch controls originating from a Eurotransplant database.

Results: From 304 AAV patients, sufficient data were available. We found DR13(6) to be less prevalent and both DR4 and the ancestral haplotype A1B8DR3 more prevalent in patients with AAV compared with controls, particularly in patients with WG. In addition, DR1 was less prevalent in patients with WG in comparison with controls. Further, DR8 was more prevalent in patients with CSS compared with other forms of vasculitis and controls. There were no associations between HLA antigens and disease characteristics or course of AAV or WG.

Conclusions: AAV is associated with increased prevalence of DR4 and the ancestral haplotype A1B8DR3 and with decreased prevalence of DR13(6), particularly in patients with WG. In patients with WG, prevalence of DR1 was decreased, whereas in patients with CSS DR8 was increased. No associations between HLA antigens and disease characteristics or course of AAV were found.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Case-Control Studies
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Granulomatosis with Polyangiitis / genetics
  • Granulomatosis with Polyangiitis / immunology
  • HLA Antigens / genetics*
  • HLA-A1 Antigen / genetics
  • HLA-B8 Antigen / genetics
  • HLA-DR Antigens / genetics
  • HLA-DR Serological Subtypes
  • HLA-DR3 Antigen / genetics
  • HLA-DR4 Antigen / genetics
  • Haplotypes
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Retrospective Studies
  • Serotyping
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Vasculitis / genetics*
  • Vasculitis / immunology*
  • Young Adult

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • HLA Antigens
  • HLA-A1 Antigen
  • HLA-B8 Antigen
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR13 antigen
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen