Publication

Checks and Balances in Autoimmune Vasculitis

Cadena, R. H., Abdulahad, W. H., Hospers, G. A. P., Wind, T. T., Boots, A. M. H., Heeringa, P. & Brouwer, E., 22-Feb-2018, In : Frontiers in Immunology. 9, 11 p., 315.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number315
Number of pages11
JournalFrontiers in Immunology
Volume9
Publication statusPublished - 22-Feb-2018

    Keywords

  • immune checkpoints, immune checkpoint inhibitors, immune-related adverse events, vasculitis, giant cell arteritis, GIANT-CELL ARTERITIS, REGULATORY T-CELLS, IMMUNE-CHECKPOINT INHIBITORS, CHRONIC VIRAL-INFECTION, CANCER-IMMUNOTHERAPY, ADVANCED MELANOMA, WEGENERS-GRANULOMATOSIS, POLYMYALGIA-RHEUMATICA, ANTI-CTLA-4 ANTIBODIES, TRYPTOPHAN CATABOLISM

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