TY - JOUR
T1 - The putative role of endoplasmic reticulum aminopeptidases in autoimmunity: insights from genomic-wide association studies
AU - Fierabracci, Alessandra
AU - Milillo, Annamaria
AU - Locatelli, Franco
AU - Fruci, Doriana
PY - 2012
Y1 - 2012
N2 - Autoimmune diseases represent a heterogeneous group of conditions whose incidence is increasing worldwide. This has stimulated studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors, aimed at finally improving prevention and treatment of these diseases. In the autoimmune process, immune responses are generated against self antigens presented by Major Histocompatibility Complex (MHC) class I on the cell surface. These peptide/MHC class I complexes are generated and assembled through MHC class I antigen processing and presentation machinery. In the endoplasmic reticulum (ER), aminopeptidases ERAP1 and ERAP2 display distinct trimming activity before antigenic peptides are loaded onto MHC class I molecules.The advent of new tools such as genome-wide association studies (GWAS) has provided evidence for new susceptibility loci and candidate genes playing a role in the autoimmune process for the recognized immune function of their transcripts. Genetic linkage has been discovered with MHC antigens and various autoimmune conditions. Recent GWAS showed the importance of ERAP1 and ERAP2 in several autoimmune diseases, including ankylosing spondylitis, insulin-dependent diabetes mellitus, psoriasis, multiple sclerosis, Crohn's disease.In this review, we first provide a general overview of ERAP1 and ERAP2 genes, their biological functions and their relevancy in autoimmunity. We then discuss the importance of GWAS and the case-control studies that confirm the relevancy of ERAP single-nucleotide polymorphism associations and their linkage with particular MHC class I haplotypes, supporting a putative functional role in the autoimmune process. (c) 2012 Elsevier B.V. All rights reserved.
AB - Autoimmune diseases represent a heterogeneous group of conditions whose incidence is increasing worldwide. This has stimulated studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors, aimed at finally improving prevention and treatment of these diseases. In the autoimmune process, immune responses are generated against self antigens presented by Major Histocompatibility Complex (MHC) class I on the cell surface. These peptide/MHC class I complexes are generated and assembled through MHC class I antigen processing and presentation machinery. In the endoplasmic reticulum (ER), aminopeptidases ERAP1 and ERAP2 display distinct trimming activity before antigenic peptides are loaded onto MHC class I molecules.The advent of new tools such as genome-wide association studies (GWAS) has provided evidence for new susceptibility loci and candidate genes playing a role in the autoimmune process for the recognized immune function of their transcripts. Genetic linkage has been discovered with MHC antigens and various autoimmune conditions. Recent GWAS showed the importance of ERAP1 and ERAP2 in several autoimmune diseases, including ankylosing spondylitis, insulin-dependent diabetes mellitus, psoriasis, multiple sclerosis, Crohn's disease.In this review, we first provide a general overview of ERAP1 and ERAP2 genes, their biological functions and their relevancy in autoimmunity. We then discuss the importance of GWAS and the case-control studies that confirm the relevancy of ERAP single-nucleotide polymorphism associations and their linkage with particular MHC class I haplotypes, supporting a putative functional role in the autoimmune process. (c) 2012 Elsevier B.V. All rights reserved.
KW - Autoimmunity etiopathogenesis
KW - MHC class 1
KW - GWAS
KW - ERAPs
KW - Antigen processing
KW - Autoimmunity etiopathogenesis
KW - MHC class 1
KW - GWAS
KW - ERAPs
KW - Antigen processing
UR - http://hdl.handle.net/10807/244434
U2 - 10.1016/j.autrev.2012.04.007
DO - 10.1016/j.autrev.2012.04.007
M3 - Article
SN - 1568-9972
VL - 12
SP - 281
EP - 288
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
ER -