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

Abstract

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.

Case of elderly onset possible neuro-Behçet’s disease with HLA-B51 homozygosity

“…Especially, in a Japanese cohort, the risk ratio was found to be 7.48 times higher in HLA-B51 carriers 13. Also, previous report showed that in various types, neuro-Beçhet’s disease have the highest rate of HLA-B51 positivity 14…”

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

“…Endoplasmic reticulum aminopeptidase 1 (ERAP1) may reflect common mechanisms with spondylarthritis by trimming the antigenic peptides to be loaded onto MHC class I molecules [ 21 ]. Although ERAP1 interacts with HLA-B51, it is not associated with vasculitis in BS [ 103 , 104 ].…”

Mycoplasma pneumoniae-Induced Rash and Mucositis (MIRM) Mimicking Behçet’s Disease and Paraneoplastic Pemphigus (PNP)

“…Thus, it has been suggested that other features might be substituted for pathergy in these populations, including aseptic meningoencephalitis, cerebral vasculitis, recurrent phlebitis, arthritis, synovitis, epididymitis, or focal bowel ulceration [ 11 ]. HLA-B ∗ 51 remains the most important genetic factor in Behçet's disease, despite the recent identification of several susceptibility genes [ 12 ]. Some patients do not meet these criteria in whom the diagnosis of Behçet's disease is still made and establishing the diagnosis in such patients is much more difficult.…”