Recent advances in our understanding of giant cell arteritis pathogenesis

• Published in: Autoimmunity reviews Vol. 16; no. 8; pp. 833 - 844
• Main Authors: Samson, Maxime, Corbera-Bellalta, Marc, Audia, Sylvain, Planas-Rigol, Ester, Martin, Laurent, Cid, Maria Cinta, Bonnotte, Bernard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2017
• Subjects: Allergy and Immunology; Animals; B-Lymphocytes - immunology; Epigenesis, Genetic; Giant cell arteritis; Giant Cell Arteritis - etiology; Giant Cell Arteritis - genetics; Giant Cell Arteritis - immunology; Humans; Infection - complications; Interferon-gamma; Interleukin-6; Interleukin-6 - immunology; Neutrophils - immunology; Receptors, Notch - immunology; T cells; Vascular remodeling; eNOS; GWAS; gene of lymphotoxin-alpha (LT-α); serum amyloid A; cluster of differentiation; MHC; platelet-derived growth factor; major histocompatibility complex; nuclear factor of activated T-cells; interleukin-6; NLR family pyrin domain containing 1; gene of lymphotoxin-beta (LT-β); CCLx; VZV; RT-PCR; TFH; severe combined-immunodeficiency; brain-derived neurotrophic factor; T helper; NADPH oxidase 2; T cell receptor; toll like receptor; intracellular adhesion molecule-1; gene of serine/threonine-protein phosphatase 2b catalytic subunit gamma isoform (PP2BC); RUNX3; BCR; regulatory T cells; lipopolysacharide; VSMC; temporal artery biopsy; dendritic cell; pathogen associated molecular pattern; DNMT1; CXCLx; methyl cpg binding protein 2; very late antigen- 4; interleukin-x; T cells; vascular remodeling; SCID; LPS; giant cell arteritis; mIL-6R; IRAK1; nerve growth factor; sIL-6R; PD-L1; anti-cardiolipin antibodies; TGF-β; NLRP1; interferon-gamma; membranous receptor of IL-6; CD; BDNF; chemokine (CC family); cytokine-induced neutrophil chemoattractant; IL-x; PAMP; VCAM-1; TAB; vascular smooth muscle cell; DC; NOX2; RUNT-related transcription factor 3; CINC; RNA; ICAM-1; PTPN22; aCL; MECP2; IFN-γ; PPP3CC; T follicular helper lymphocytes; Th; SNPs; endothelial nitric oxide synthase; iNOS; single nucleotide polymorphisms; chemokine receptor (CXC family); interferon gamma; LFA-1; human leukocyte antigen; NGF; polymyalgia rheumatica; MMP; SAA; ET-1; CRH; LTA; interleukin-1 receptor-associated kinase 1; lymphocyte function-associated antigen 1; CXCR; LTB; HLA; gene of plasminogen; PD-1; ribonucleic acid; TCR; transforming growth factor beta; metalloproteinase; PLG; B-cell receptor; vascular cell adhesion molecule-1; chemokine (CXC family); NFAT; HIF-1; deoxyribonucleic acid; tumor necrosis factor alpha; induced NO-synthase; programmed death-1; TLR; endothelin-1; soluble receptor of IL-6; corticotropin-releasing hormone; GCA; NOS2; VEGF; STAT3; Treg; chemokine receptor (CC family); programmed death-ligand 1; signal transducer and activator of transcription 3; VLA-4; protein tyrosine phosphatase, non-receptor type 22; CCR; PMR; TNF-α; DNA; PDGF; vascular endothelial growth factor; genome-wide association study; hypoxia-inducible factor-1; nitric oxide synthase 2; reverse transcription polymerase chain reaction; varicella zoster virus; DNA methyltransferase 1; Vascular remodeling; Interleukin-6; Interferon-gamma; Giant cell arteritis
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2017.05.014

Abstract Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4+ T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8+ T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling.