Takayasu arteritis: a geographically distant but immunologically proximal MHC-I-opathy
Abstract
Takayasu arteritis, a granulomatosis vasculitis with a pathogenesis that is poorly defined but known to be associated with HLA-B*52, shares many features with other MHC-I-opathies. In addition to the shared clinical features of inflammatory bowel diseases, cutaneous inflammation, and HLA-B*52, is shared association of an IL12B single- nucleotide polymorphism encoding the common IL-12 and IL-23 p40 subunit, which might affect not only type 17 cytokine responses, but also IFNgamma and TNF production-the cardinal type 1 cytokines in granuloma formation. Considering the translational context of responses to TNF inhibition in Takayasu arteritis, in this Personal View we propose Takayasu arteritis as a type 1 MHC-I-opathy. Additionally, type 1 and type 17 T-cell immune responses show immune plasticity, which connects the overlapping features of Takayasu arteritis and spondyloarthritis spectrum disorders, providing a basis for shared anti-TNF responses, and points to p40 and IFNgamma cytokine antagonism and potential selective CD8 T-cell repertoire ablation.