title: Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis.
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.
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Marjan C
authors.initials: MC
authors.lastname: Slot
authors.forename: Milena G
authors.initials: MG
authors.lastname: Sokolowska
authors.forename: Kim G
authors.initials: KG
authors.lastname: Savelkouls
authors.forename: Rob G J H
authors.initials: RG
authors.lastname: Janssen
authors.forename: Jan G M C
authors.initials: JG
authors.lastname: Damoiseaux
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000235:genetics* / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014657:Vasculitis / Q000235:genetics* / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor