Towards a basis for vascular versus intestinal phenotype differences; East Meets West in Behcet's disease.

Phenotypic differences in disease expression across ethnic populations may hold the key to a better understanding of the pathophysiology of Behçet's disease (BD), which has a wide geographical distribution and marked clinical variability between East Asian, Middle Eastern, and Western countries. In contrast to the predominance of vascular involvement in regions such as Turkey, intestinal involvement is more frequently observed in East Asian patients, particularly in Japan. Genome-wide association studies in inflammatory bowel disease (IBD), which shows clinical similarity to BD, have identified NOD2 and IL23R variants as major susceptibility loci in European populations. However, the relative absence of these IBD-related variants in East Asian populations, where intestinal BD is more prevalent, suggests the presence of alternative, BD-specific mechanisms driving gut involvement in different genetic backgrounds. Herein, we argue that this diversity in BD clinical expression may also reflect underlying differences in innate immune responses, particularly involving IL-1 signaling pathways. The striking prominence of