New insights into the pathogenesis of Behçet's disease

Abstract

Behçet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic [1,2] and immunology [3] of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy.