[Physiopathology of giant cell arteritis: From inflammation to vascular remodeling]

Abstract

Giant cell arteritis (GCA) is a large-vessel vasculitis involving the aorta and its main branches, especially supra aortic branches. Although much progress has been made, the pathophysiology remains incompletely understood. An initial trigger, suspected of infectious origin, lead to the maturation and recruitment of dendritic cells (DC). The lack of migration of these DC allows the local recruitment of T-lymphocytes (LT). These LT- CD4⁺ polarize in Type 1 helper (Th1), Th17 but also Th9. A qualitative and quantitative deficit in regulatory T cells (Treg) is observed under the influence of IL-21 overproduction. In addition, an imbalance in the Th17/Treg balance is favored by IL-6. The secretion of IFN-γ, IL-17, IL-6, IL-33 is responsible for a sustained local inflammatory reaction that is organized around tertiary lymphoid follicles. Locally recruited macrophages secrete reactive forms of oxygen together with VEGF and PDGF. These growth factors, together with neurotrophins and endothelin contribute to increase the proliferation of vascular smooth muscle cells (VSMCs). The imbalance between matrix metalloproteases (MMP)-2, MMP-9 and MMP-14 and tissue inhibitors of metalloproteases (TIMP)-1 and TIMP-2 also contribute to the remodeling process occurring in the vessel wall. Finally, arterial neovascularization contribute to the perpetuation of lymphocyte recruitment. This persistent remodeling is sometimes complicated by ischemic events responsible for the initial severity of the disease.