Investigation of type I interferon responses in ANCA-associated vasculitis.pdf (3.04 MB)
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Investigation of type I interferon responses in ANCA-associated vasculitis

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posted on 08.06.2022, 15:17 by Isabella Batten, Mark W Robinson, Arthur White, Cathal Walsh, Barbara Fazekas, Jason Wyse, Antonia Buettner, Suzanne D’Arcy, Emily GreenanEmily Greenan, Conor MurphyConor Murphy, Zoe Wigston, Joan Ni Gabhann-DromgooleJoan Ni Gabhann-Dromgoole, Edward M Vital, Mark A Little, Nollaig M Bourke
Type I interferon (IFN) dysregulation is a major contributory factor in the development of several autoimmune diseases, termed type I interferonopathies, and is thought to be the pathogenic link with chronic inflammation in these conditions. Anti-neutrophil cytoplasmic antibody (ANCA)-Associated Vasculitis (AAV) is an autoimmune disease characterised by necrotising inflammation of small blood vessels. The underlying biology of AAV is not well understood, however several studies have noted abnormalities in type I IFN responses. We hypothesised that type I IFN responses are systemically dysregulated in AAV, consistent with features of a type I interferonopathy. To investigate this, we measured the expression of seven interferon regulated genes (IRGs) (ISG15, SIGLEC1, STAT1, RSAD2, IFI27, IFI44L and IFIT1) in peripheral blood samples, as well as three type I IFN regulated proteins (CXCL10, MCP-1 and CCL19) in serum samples from AAV patients, healthy controls and disease controls. We found no difference in type I IFN regulated gene or protein expression between AAV patients and healthy controls. Furthermore, IRG and IFN regulated protein expression did not correlate with clinical measurements of disease activity in AAV patients. Thus, we conclude that systemic type I IFN responses are not key drivers of AAV pathogenesis and AAV should not be considered a type I interferonopathy.

Funding

Science Foundation Ireland Grant 11/Y/B2093

Meath Foundation Grant 208591

History

Comments

The original article is available at https://www.nature.com/articles

Published Citation

Batten I. et al. Investigation of type I interferon responses in ANCA-associated vasculitis. Sci Rep. 2021;11(1):8272

Publication Date

15 April 2021

PubMed ID

33859290

Department/Unit

  • Ophthalmology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Immunity, Infection and Inflammation
  • Surgical Science and Practice
  • Biomaterials and Regenerative Medicine
  • Chemistry and Pharmaceutical Sciences
  • Health Professions Education

Publisher

Springer Science and Business Media LLC

Version

  • Published Version (Version of Record)