Giant cell arteritis: update on pathogenesis and clinical implications

Abstract

Purpose of review: Giant cell arteritis (GCA) is an age-related autoimmune disease with a complex pathogenesis that involves several pathogenic mechanisms. This review provides recent critical insights into novel aspects of GCA pathogenesis.

Recent findings: The use of novel approaches, including multiomic techniques, has uncovered notable findings that broaden the understanding of GCA pathogenesis. TCF1hiCD4+ T cells have been identified as stem-like T cells residing in tertiary lymphoid structures in the adventitia of GCA aortic tissues, which likely supply the pathogenic effector T cells present in vasculitic lesions. Studies have demonstrated that fibroblasts present in GCA-inflamed arteries are not innocent bystanders, but they contribute to arterial inflammation via maintenance of Th1 and Th17 polarisation, cytokine secretion (IL-6, IL-1B, IL-12, and IL-23) and antigen presentation. Additionally, deregulated cellular senescence programs are present in GCA as an accumulation of IL-6 and matrix metalloproteinase 9-producing senescent cells have been identified in vasculitic lesions.

Summary: Recent studies have unravelled interesting findings with potentially significant clinical relevance. Stem-like T cells are likely key contributors to vascular disease persistence, and targeted depletion or modulation of these cells holds promise in GCA management. Fibroblast-targeting therapies and senotherapeutics are also exciting prospects in the treatment of GCA.