The genetics of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complex area of investigation because of the low frequency of AAVs, the rarity of familial cases and the complexity of disease phenotypes. However, recent studies have been able to gather significant numbers of patients, and multicentre collaborative efforts have allowed the performance of two genome-wide association studies (GWASs). Genetic association studies based on candidate gene approaches and the two GWASs have greatly contributed to our current understanding of the genetic basis of AAV. The central role of autoimmunity has been confirmed by the significant association with HLA polymorphisms; interestingly, the three main AAV subtypes are associated with distinct HLA variants, i.e. granulomatosis with polyangiitis (Wegener's GPA) with HLA-DP1, microscopic polyangiitis with HLA-DQ and eosinophilic GPA (Churg-Strauss) with HLA-DRB4. GWASs also revealed that polymorphic variants of genes encoding proteinase 3 (PR3), the predominant antigenic target of ANCA in GPA, and its main inhibitor, alpha-1 antitrypsin, are highly associated with GPA and, even more significantly, with PR3-ANCA positivity (regardless of the clinical diagnosis); this emphasizes the central pathogenic role of PR3 and humoral autoimmunity in PR3-ANCA positive vasculitis. Finally, candidate gene approach studies have shown associations with other variants involved in autoimmunity, such as those belonging to the CTLA-4 and PTPN22 genes, although these findings warrant replication in larger studies. Additional studies are underway to better characterize disease associations within the AAV spectrum, which could provide new pathogenetic clues and possibly new treatment targets.
Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis / F. Alberici, D. Martorana, A. Vaglio. - In: NEPHROLOGY DIALYSIS TRANSPLANTATION. - ISSN 0931-0509. - 30:suppl. 1(2015 Apr), pp. 37-45.
|Titolo:||Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis|
ALBERICI, FEDERICO (Primo)
|Parole Chiave:||ANCA; HLA; PTPN22; vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Autoimmunity; Humans; Genome-Wide Association Study|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||apr-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/ndt/gfu386|
|Appare nelle tipologie:||01 - Articolo su periodico|