Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

Makkuni, Damodar; Bharadwaj, Aditya; Wolfe, Konrad; Payne, Susan N.; Hutchings, Andrew; Dasgupta, Bhaskar

doi:10.1093/rheumatology/ken012

Cited by 54 publications

(35 citation statements)

References 14 publications

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“…Ultimately, the remodeling of the arterial wall causes luminal compromise and gives rise to the ischemic complications of GCA, including blindness, stroke, and aortic arch syndrome (37). We explored whether the enrichment of PD-1 + T cells in the mural infiltrates has consequences for the outgrowth of new microvessels and for the expansion of the intimal layer.…”

Section: Pd-1 Checkpoint Inhibition Selects For Proinflammatory T Cellsmentioning

confidence: 99%

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

Zhang

Watanabe

Berry

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

189

203

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Giant cell arteritis (GCA) causes autoimmune inflammation of the aorta and its large branches, resulting in aortic arch syndrome, blindness, and stroke. CD4+ T cells and macrophages form organized granulomatous lesions in the walls of affected arteries, destroy the tunica media, and induce ischemic organ damage through rapid intimal hyperplasia and luminal occlusion. Pathogenic mechanisms remain insufficiently understood; specifically, it is unknown whether the unopposed activation of the immune system is because of deficiency of immunoinhibitory checkpoints. Transcriptome analysis of GCA-affected temporal arteries revealed low expression of the coinhibitory ligand programmed death ligand-1 (PD-L1) concurrent with enrichment of the programmed death-1 (PD-1) receptor. Tissue-residing and ex vivo-generated dendritic cells (DC) from GCA patients were PD-L1 lo

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Section: Pd-1 Checkpoint Inhibition Selects For Proinflammatory T Cellsmentioning

confidence: 99%

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

Zhang

Watanabe

Berry

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

189

203

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“…Multinucleated giant cells produce vascular endothelial growth factor (VEGF), which is required with platelet-derived growth factor (PDGF) for angiogenesis in the hyperplastic intima [37]. In GCA, the new vessels appear in the media and intima, whereas in normal arteries the vasa vasorum is evident in the adventitia layer only [38]. The number of vessels correlates with the degree of intimal hyperplasia and the degree of luminal stenosis has been closely linked to PDGF signalling [39].…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Giant Cell Arteritis: Beyond Corticosteroids

2015

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Giant cell arteritis (GCA) is a large-vessel vasculitis predominantly affecting older people, with a peak incidence between 70 and 79 years of age. If untreated, ischaemic complications can be catastrophic for the patient, including blindness. We review the current treatment paradigms for this condition, the mainstay of which is immediate high-dose glucocorticoid therapy with a gradual dose tapering. Adverse events of glucocorticoid therapy are often observed after 12-24 months and corticosteroid-sparing adjuvant therapies are used in severe disease, multiple flares or patients at high risk of prolonged therapy. The current understanding of the pathogenesis of GCA is explored. This has informed the identification of new potential targets and approaches to treatment. Blockade of interleukin (IL)-6 (tocilizumab) and IL-1 (gevokizumab) are being evaluated in phase III clinical trials. It is hoped that improved risk stratification of organ damage and relapses will be developed using imaging and biomarkers, allowing for individualised treatment for patients; however, there remains further work to be done before this becomes a reality.

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“…25 Normal arteries have avascular media and intima with a capillary network, or vasa vasorum, only in the adventitia. 16 In GCA the new capillaries appear primarily in the media and intima and are more numerous in arteries with advanced intimal hyperplasia that result in luminal stenosis. 14…”

Section: Histopathology Of Gcamentioning

confidence: 99%

Giant Cell Arteritis and Angiogenesis: A Review

Mitchell

Cestari

2009

Seminars in Ophthalmology

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Giant cell arteritis is a vasculitis of large and medium sized arteries with variable clinical presentations. Arteritic anterior ischemic optic neuropathy is the most common cause of visual loss from giant cell arteritis and the ischemia related to this process is presumed to be secondary to luminal stenosis from intimal hyperplasia. This process has been found to be initiated and promoted by various inflammatory and pro-angiogenic factors.

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Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

Cited by 54 publications

References 14 publications

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

Giant Cell Arteritis: Beyond Corticosteroids

Giant Cell Arteritis and Angiogenesis: A Review

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