Takayasu arteritis: a geographically distant but immunologically proximal MHC-I-opathy. [Review]
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All Authors
Abacar, K.
Macleod, T.
Direskeneli, H.
McGonagle, D.
LTHT Author
Abacar, Kerem
Macleod, Tom
McGonagle, Dennis
Macleod, Tom
McGonagle, Dennis
LTHT Department
NIHR Leeds Biomedical Research Centre
Rheumatology
Rheumatology
Non Medic
Publication Date
2025
Item Type
Journal Article
Review
Review
Language
Subject
Subject Headings
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.
Journal
The Lancet Rheumatology