. 2018 Mar; 9:315.
doi: 10.3389/fimmu.2018.00315.

Checks and Balances in Autoimmune Vasculitis

Rebeca Hid Cadena 1 Wayel H Abdulahad 1 G A P Hospers 2 T T Wind 2 Annemieke M H Boots 3 Peter Heeringa 1 Elisabeth Brouwer 3 
  • PMID: 29520282
  •     105 References
  •     16 citations


Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system. The use of immune checkpoint inhibitors (ICIs) to treat cancer has proven to be effective producing durable antitumor responses in multiple cancer types. However, one of the disadvantages derived from the use of these agents is the appearance of inflammatory manifestations termed immune-related adverse events (irAEs). These irAEs are often relatively mild, but more severe irAEs have been reported as well including several forms of vasculitis. In this article, we argue that age-related changes in expression and function of immune checkpoint molecules lead to an unstable immune system, which is prone to tolerance failure and autoimmune vasculitis development. The topic is introduced by a case report from our hospital describing a melanoma patient treated with ICIs and who subsequently developed biopsy-proven giant cell arteritis. Following this case report, we present an in-depth review on the role of immune checkpoint pathways in the development and progression of autoimmune vasculitis and its relation with an aging immune system.

Keywords: giant cell arteritis; immune checkpoint inhibitors; immune checkpoints; immune-related adverse events; vasculitis.

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Extracellular vesicles in autoimmune vasculitis - Little dirts light the fire in blood vessels.
Xiuhua Wu, Yu Liu, Wei Wei, Ming-Lin Liu.
Autoimmun Rev, 2019 Apr 09; 18(6). PMID: 30959208    Free PMC article.
Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.
L K Brekke, B-T S Fevang, +3 authors, C G Gjesdal.
Arthritis Res Ther, 2019 Jun 27; 21(1). PMID: 31238961    Free PMC article.
Decreased Expression of Negative Immune Checkpoint VISTA by CD4+ T Cells Facilitates T Helper 1, T Helper 17, and T Follicular Helper Lineage Differentiation in GCA.
Rebeca Hid Cadena, Rosanne D Reitsema, +6 authors, Elisabeth Brouwer.
Front Immunol, 2019 Aug 06; 10. PMID: 31379838    Free PMC article.
Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors.
Konstantinos Melissaropoulos, Kalliopi Klavdianou, +3 authors, Dimitrios Daoussis.
Int J Mol Sci, 2020 May 15; 21(9). PMID: 32403289    Free PMC article.
Immunotherapies and Combination Strategies for Immuno-Oncology.
Cody Barbari, Tyler Fontaine, +4 authors, Rahul R Deshmukh.
Int J Mol Sci, 2020 Jul 19; 21(14). PMID: 32679922    Free PMC article.
Cardiovascular immune-related adverse events: Evaluation, diagnosis and management.
Yingxian Liu, Wei Wu.
Asia Pac J Clin Oncol, 2020 Mar 05; 16(4). PMID: 32129935    Free PMC article.
Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review.
Caberry W Yu, Matthew Yau, +2 authors, Jonathan A Micieli.
Eye Brain, 2020 Nov 12; 12. PMID: 33173368    Free PMC article.
EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.
Marie Kostine, Axel Finckh, +20 authors, Thierry Schaeverbeke.
Ann Rheum Dis, 2020 Apr 25; 80(1). PMID: 32327425    Free PMC article.
PD-1/PDL-1 Inhibitors and Cardiotoxicity; Molecular, Etiological and Management Outlines.
Mohammed Safi, Hyat Ahmed, +6 authors, Jiwei Liu.
J Adv Res, 2021 Apr 13; 29. PMID: 33842004    Free PMC article.
Rheumatic immune-related adverse events induced by immune checkpoint inhibitors.
Hui Zhong, Jiaxin Zhou, Dong Xu, Xiaofeng Zeng.
Asia Pac J Clin Oncol, 2020 Jul 28; 17(3). PMID: 32717098    Free PMC article.
Myocardial Vasculitis Associated With the Immune Checkpoint Inhibitor Pembrolizumab.
Hideo Oishi, Ryota Morimoto, +7 authors, Toyoaki Murohara.
JACC Case Rep, 2021 Jul 29; 2(12). PMID: 34317084    Free PMC article.
Immune Checkpoint Inhibitors and the Heart.
Diana Larisa Mocan-Hognogi, Sebastian Trancǎ, +3 authors, Anca Simona Bojan.
Front Cardiovasc Med, 2021 Oct 19; 8. PMID: 34660728    Free PMC article.
Recent advances in Extracellular Vesicles and their involvements in vasculitis.
Nan Yang, Yin Zhao, +4 authors, Ming-Lin Liu.
Free Radic Biol Med, 2021 May 06; 171. PMID: 33951487    Free PMC article.