Pathogenesis of giant cell (temporal) arteritis
- Gene G Hunder, MD
Gene G Hunder, MD
- Section Editor — Vasculitis
- Emeritus Consultant
- Professor Emeritus
- Mayo Clinic College of Medicine
Giant cell (temporal) arteritis (GCA) is a chronic vasculitis of large- and medium-sized vessels, which occurs among individuals over 50 years of age . Although it may be generalized, vessel inflammation most prominently involves the cranial branches of the arteries originating from the aortic arch [2,3].
This topic will review the pathogenesis of GCA. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Clinical manifestations of giant cell (temporal) arteritis" and "Diagnosis of giant cell (temporal) arteritis" and "Treatment of giant cell (temporal) arteritis".)
ETIOLOGY AND PATHOGENESIS
The etiology and pathogenesis of giant cell (temporal) arteritis (GCA) are unknown. However, the following observations suggest that increasing age, a unique genetic and ethnic background, and infection may have causative roles [4,5].
●GCA occurs with increased frequency among individuals older than 50 years of age. Specific age-related changes in the innate and adaptive immune systems and age-related alterations of large and medium blood vessels appear important in the development of the vasculitis .
●Clustering of the illness may occur within families .
- Hellmann DB, Hunder GG. Giant cell arteritis and polymyalgia rheumatica. In: Kelley's Textbook of Rheumatology, 7th, Harris ED, Budd RC, Firestein GS, Genovese MC, et al (Eds), WB Saunders Company, Philadelphia 2005.
- Evans JM, Bowles CA, Bjornsson J, et al. Thoracic aortic aneurysm and rupture in giant cell arteritis. A descriptive study of 41 cases. Arthritis Rheum 1994; 37:1539.
- Klein RG, Hunder GG, Stanson AW, Sheps SG. Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 1975; 83:806.
- Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003; 349:160.
- Kaiser M, Weyand CM, Björnsson J, Goronzy JJ. Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis. Arthritis Rheum 1998; 41:623.
- Mohan SV, Liao YJ, Kim JW, et al. Giant cell arteritis: immune and vascular aging as disease risk factors. Arthritis Res Ther 2011; 13:231.
- Mathewson JA, Hunder GG. Giant cell arteritis in two brothers. J Rheumatol 1986; 13:190.
- Duhaut P, Pinede L, Demolombe-Rague S, et al. Giant cell arteritis and cardiovascular risk factors: a multicenter, prospective case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes. Arthritis Rheum 1998; 41:1960.
- Salvarani C, Gabriel SE, O'Fallon WM, Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med 1995; 123:192.
- Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. The HLA-DRB1 locus as a genetic component in giant cell arteritis. Mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule. J Clin Invest 1992; 90:2355.
- Weyand CM, Hunder NN, Hicok KC, et al. HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis. Arthritis Rheum 1994; 37:514.
- Salvarani C, Casali B, Boiardi L, et al. Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity. J Rheumatol 2000; 27:1215.
- Mattey DL, Hajeer AH, Dababneh A, et al. Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms. Arthritis Rheum 2000; 43:1749.
- Boiardi L, Casali B, Nicoli D, et al. Vascular endothelial growth factor gene polymorphisms in giant cell arteritis. J Rheumatol 2003; 30:2160.
- Salvarani C, Casali B, Farnetti E, et al. PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis. Arthritis Rheum 2007; 56:3502.
- Gabriel SE, Espy M, Erdman DD, et al. The role of parvovirus B19 in the pathogenesis of giant cell arteritis: a preliminary evaluation. Arthritis Rheum 1999; 42:1255.
- Wagner AD, Gérard HC, Fresemann T, et al. Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with the topographic arrangement of tissue-infiltrating dendritic cells. Arthritis Rheum 2000; 43:1543.
- Haugeberg G, Bie R, Nordbø SA. Temporal arteritis associated with Chlamydia pneumoniae DNA detected in an artery specimen. J Rheumatol 2001; 28:1738.
- Mitchell BM, Font RL. Detection of varicella zoster virus DNA in some patients with giant cell arteritis. Invest Ophthalmol Vis Sci 2001; 42:2572.
- Nagel MA, Khmeleva N, Boyer PJ, et al. Varicella zoster virus in the temporal artery of a patient with giant cell arteritis. J Neurol Sci 2013; 335:228.
- Gilden D, White T, Khmeleva N, et al. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology 2015; 84:1948.
- Papaioannou CC, Gupta RC, Hunder GG, McDuffie FC. Circulating immune complexes in giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum 1980; 23:1021.
- Lie JT. Histopathologic specificity of systemic vasculitis. Rheum Dis Clin North Am 1995; 21:883.
- Weyand CM, Goronzy JJ. Arterial wall injury in giant cell arteritis. Arthritis Rheum 1999; 42:844.
- Martinez-Taboada VM, Goronzy JJ, Weyand CM. Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis. Clin Immunol Immunopathol 1996; 79:263.
- Roche NE, Fulbright JW, Wagner AD, et al. Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum 1993; 36:1286.
- Brack A, Rittner HL, Younge BR, et al. Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. J Clin Invest 1997; 99:2842.
- Ma-Krupa W, Jeon MS, Spoerl S, et al. Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J Exp Med 2004; 199:173.
- Weyand CM, Tetzlaff N, Björnsson J, et al. Disease patterns and tissue cytokine profiles in giant cell arteritis. Arthritis Rheum 1997; 40:19.
- Piggott K, Biousse V, Newman NJ, et al. Vascular damage in giant cell arteritis. Autoimmunity 2009; 42:596.
- Weyand CM, Younge BR, Goronzy JJ. IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis. Curr Opin Rheumatol 2011; 23:43.