Four inflammatory diseases are strongly associated with Major Histocompatibility Complex class I (MHC-I) molecules: birdshot chorioretinopathy (HLA-A<sup>*</sup>29:02), ankylosing spondylitis (HLA-B<sup>*</sup>27), Behçet's disease (HLA-B<sup>*</sup>51), and psoriasis (HLA-C<sup>*</sup>06:02).
Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behçet's disease and psoriasis, respectively.
In this Perspectives article, we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B(*)51, HLA-C(*)0602 and HLA-B(*)27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis.
Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease.
Data suggest that other HLA (HLA-C, HLA-DR) and HLA-related [MHC Class I chain-related gene A (MIC-A), TNF-α] genes may play a role in BD co-susceptibility or pathogenesis.
HLA-C genotyping by the PCR-SSP method also suggests that the BD pathogenic gene is not the HLA-C gene itself but other gene located near the HLA-B gene.
These facts suggest that the pathogenic gene of Behçet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA-Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the centromeric side of the HLA-B gene rather than in the telomeric side around the HLA-C gene.