Checks and Balances in Autoimmune Vasculitis

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 check...

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Bibliographic Details
Published in:Frontiers in immunology 2018-02, Vol.9, p.315-315
Main Authors: Hid Cadena, Rebeca, Abdulahad, Wayel H, Hospers, G A P, Wind, T T, Boots, Annemieke M H, Heeringa, Peter, Brouwer, Elisabeth
Format: Article
Language:English
Subjects:
giant cell arteritis
immune checkpoint inhibitors
immune checkpoints
immune-related adverse events
Immunology
vasculitis
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.00315