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The Aging Immune System and Health

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Front. Immunol. | doi: 10.3389/fimmu.2018.00315

Checks and Balances in Autoimmune Vasculitis

  • 1Department of Pathology & Medical Biology, University Medical Center Groningen, Netherlands
  • 2Department of Rheumatology & Clinical Immunology, University Medical Center Groningen, Netherlands

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 co-inhibitory and co-stimulatory 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 anti-tumor 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 ageing immune system.

Keywords: immune checkpoints, immune checkpoint inhibitors, immune related adverse events (irAEs), Vasculitis, Giant Cell Arteritis

Received: 09 Nov 2017; Accepted: 05 Feb 2018.

Edited by:

Patrizia Rovere Querini, Vita-Salute San Raffaele University, Italy

Reviewed by:

Ralf J. Ludwig, University of Lübeck, Germany
Augusto Vaglio, Università degli Studi di Parma, Italy  

Copyright: © 2018 Hid Cadena, Abdulahad, Boots, Heeringa and Brouwer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Wayel H. Abdulahad, University Medical Center Groningen, Department of Pathology & Medical Biology, Hanzeplein 1, Groningen, 9713 GZ, Netherlands, w.abdulahad@umcg.nl