The association of Behçet's syndrome with HLA-B51 as understood in 2021.

PURPOSE OF REVIEW: To discuss clinical and pathogenic roles of HLA-B∗51 in Behçet's syndrome.

RECENT FINDINGS: HLA-B∗51 remains the most important genetic factor in Behçet's syndrome, despite the recent identification of several susceptibility genes. The prevalence of HLA-B∗51 has been shown to differ among phenotype-based clinical clusters in the same patient population. HLA-B∗51 shows epistatic interaction with the susceptible allele of endoplasmic reticulum aminopeptidase (ERAP)1 encoding the Hap10 allotype, which has the lowest trimming activity of the MHC-Class I binding peptides. Subsequent molecular studies have suggested that the disease-associated Hap10 allotype is implicated in the generation and selection of the disease protective or promoting peptides loading onto HLA-B∗51, although these pathogenic peptides have yet to be identified.

SUMMARY: HLA-B∗51 is a hallmark of Behçet's syndrome but genetic markers are not very useful in the diagnosis of Behçet's syndrome. Rather, it is considered an important factor in determining clinical phenotypes in this heterogeneous condition. The epigenetic interaction of HLA-B∗51 with ERAP1 sheds light on pathogenesis.