Behçet disease (BD) and BD-like clinical phenotypes: NF-kB pathway in mucosal ulcerating diseases

Sandro F Perazzio 1 2, Eric J Allenspach 1, Kari K Eklund 3 4, Markku Varjosalo 3 5 4, Michi M Shinohara 6, Troy R Torgerson 7, Mikko R J Seppänen 8

Affiliations

PMID: 32889730
DOI: 10.1111/sji.12973

Abstract

Behçet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namely HLA-B*51, ERAP1, IL-10, IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNFa, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-kB activation (e.g. TNFAIP3, NFKB1, OTULIN, RELA, IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-kB pathway suggesting new elements in the elusive BD etiopathogenesis.

Keywords: Behçet’s disease; HLA-B51; IKBKB; IKBKG; NF-kB pathway; NFKB1; RELA; TNFAIP3; autoinflammatory syndrome; chromosome 8 trisomy; phagocytes.