Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis

Clin Immunol. 2008 Jul;128(1):39-45. doi: 10.1016/j.clim.2008.03.506. Epub 2008 Apr 29.

Abstract

T cell activation is regulated by inhibitory molecules such as PD-1 and CTLA-4, whose expression may be affected by gene polymorphisms. Increased T cell activation is present in patients with ANCA-associated vasculitis (AAV). We investigated two single-nucleotide polymorphisms (SNPs) in PDCD1 and five polymorphisms in CTLA4 in 102 patients with AAV and 188 healthy controls (HC). The distributions of the PD-1.3 and PD-1.5 SNPs, and the distributions of the CTLA4 promoter polymorphisms -1722T/C, -1661A/G, -318 C/T, and the (AT)(n) microsatellite in the 3'-untranslated region of CTLA4, did not differ between patients and HC. However, the +49 G allele was significantly more often present in patients with AAV. Furthermore, the co-occurrence of the PD-1.5 T allele with CTLA4 +49 AA homozygosity (i.e., the absence of a G allele) was less often present in patients compared to HC. These genetic polymorphisms may lead to hyperreactivity of T cells and thus may contribute to the pathogenesis of AAV.

MeSH terms

  • Adult
  • Antibodies, Antineutrophil Cytoplasmic / genetics*
  • Antibodies, Antineutrophil Cytoplasmic / immunology
  • Antigens, CD / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • CTLA-4 Antigen
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Lymphocyte Activation / physiology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Programmed Cell Death 1 Receptor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vasculitis / genetics*
  • Vasculitis / immunology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor