Jörg J. Goronzy

59 – Large-vessel vasculitides

Abstract Large-vessel vasculitides (LVVs) include giant-cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatic (PMR). Dendritic cells (DCs), T cells, and macrophages, arranged in transmural infiltrates in medium and large arteries, cause the vascular pathology. Vascular GCA is now recognized as a chronic and persistent lesion, which is characterized by a defect in the inhibitory programmed death 1 (PD-1) immune checkpoint. Extravascular GCA results from innate immune activation and an intense hepatic acute phase response. Emerging data suggest partial autonomy of vascular and extravascular disease with respect to pathogenesis, course, and therapeutic responsiveness. A newly described immune aging signature implicates a defect in CD8 regulatory T cells (Tregs) in controlling the overall size and activity of the CD4 T-cell compartment. Tissue biopsy remains the single most valuable diagnostic procedure. Many patients require chronic immunosuppression. Noninvasive imaging modalities are critically important in monitoring for disease progression. With the advent of new biologicals blocking cytokine function and costimulatory signals, the therapeutic armamentarium is broadening, but efficacy in suppressing vascular lesions remains unresolved.