Takayasu's arteritis (TA) is a chronic large vessel
vasculitis. The physiopathology of TA has not been completely elucidated, but it appears to be multifactorial and to mainly involve cellular immunity. The pathologic sequence could implicate stimulation from an
antigen that triggers
heat shock protein (HSP)-65 expression in aortic tissue which, in turn, induces
MHC class I-related chain A (
MICA). T-cells and natural killer (NK) cells expressing NKG2D receptors could recognize
MICA, resulting in acute
inflammation. Pro-inflammatory
cytokines released from these infiltrating cells induce
matrix metalloproteinases and amplify the inflammatory response, inducing more MHC
antigen and costimulatory molecule expression on vascular cells and, thus, recruiting more mononuclear cells. Alpha-beta T-cells then infiltrate and specifically recognize one or a few
autoantigens presented by a shared
epitope associated with specific MHC on the dendritic cells (DC). These DC simultaneously cooperate to some extent with B-cells and determine a humoral immunity mainly constituted by anti-endothelial cell
autoantibodies that could trigger
complement-dependent cytotoxicity against endothelial cells. The use of
corticosteroids and of other
immunosuppressive agents can bring TA into remission in most patients. A better understanding of the immunological mechanisms responsible for the
vascular injury has led to trials of anti-
TNF-alpha agents with encouraging results. In the near future, new drugs specifically designed to target some of the mechanisms described above may be able to expand the physician's therapeutic arsenal in TA.