Is Behçet's disease a ‘class 1‐opathy’? The role of HLA‐B*51 in the pathogenesis of Behçet's disease

Summary The association between carriage of the human leucocyte antigen (HLA)‐B*51 allele and development of Behçet's disease (BD) has been known since the early 1970s, but the exact mechanisms responsible for its role in pathogenesis remain much‐debated. In an effort to explain the disease process, it has been suggested that BD constitutes one of a newly termed group of diseases, the ‘MHC‐I‐opathies’. Other MHC‐I‐opathies include ankylosing spondylitis and HLA‐B*27‐associated spondyloarthropathies and HLA‐C*0602‐associated skin psoriasis. Recent work analysing the peptidome of HLA‐B*51 suggests that altered peptide presentation by HLA‐B*51 is vital to the disease process. In this review, we argue that immune receptor interactions with HLA‐B*51 or the HLA‐B*51‐peptide complex could lead to development of inflammation in BD. The evidence for CD8 + T cell involvement is weak, and based on emerging studies it seems more likely that natural killer (NK) or other cell interactions, perhaps mediated by leucocyte immunoglobulin‐like receptor (LILR) or killer immunoglobulin‐like receptor (KIR) receptors, are culpable in pathogenesis. HLA misfolding leading directly to inflammation is another hypothesis for BD pathogenesis that deserves greater investigation. Ultimately, greater understanding of HLA‐B*51's unique role in BD will probably lead to improved development of therapeutic strategies.