Investigation of type I interferon responses in ANCA-associated vasculitis

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 Vas...

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Bibliographic Details
Published in:Scientific reports 2021-04, Vol.11 (1), p.8272-8272, Article 8272
Main Authors: Batten, Isabella, Robinson, Mark W., White, Arthur, Walsh, Cathal, Fazekas, Barbara, Wyse, Jason, Buettner, Antonia, D’Arcy, Suzanne, Greenan, Emily, Murphy, Conor C., Wigston, Zoe, Gabhann-Dromgoole, Joan Ní, Vital, Edward M., Little, Mark A., Bourke, Nollaig M.
Format: Article
Language:English
Subjects:
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Antineutrophil cytoplasmic antibodies
Autoimmune diseases
Blood vessels
CCL19 protein
CXCL10 protein
Disease
Humanities and Social Sciences
Inflammation
Interferon
Leukocytes (neutrophilic)
Monocyte chemoattractant protein 1
multidisciplinary
Peripheral blood
Protein expression
Science
Science (multidisciplinary)
Stat1 protein
Vasculitis
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-87760-4