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Abstract
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.
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1 Trinity Translational Medicine Institute, Trinity College Dublin, Department of Medical Gerontology, School of Medicine, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705)
2 Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Department of Biology, Kildare, Ireland (GRID:grid.95004.38) (ISNI:0000 0000 9331 9029)
3 Trinity College Dublin, School of Computer Science and Statistics, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705)
4 University of Limerick, Department of Mathematics and Statistics, Limerick, Ireland (GRID:grid.10049.3c) (ISNI:0000 0004 1936 9692)
5 National University of Ireland Galway, Regenerative Medicine Institute (REMEDI), School of Medicine, Galway, Ireland (GRID:grid.6142.1) (ISNI:0000 0004 0488 0789)
6 Trinity College Dublin, Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705)
7 Royal College of Surgeons in Ireland, Department of Ophthalmology, Dublin 2, Ireland (GRID:grid.4912.e) (ISNI:0000 0004 0488 7120); Royal Victoria Eye and Ear Hospital, Department of Ophthalmology, Dublin 2, Ireland (GRID:grid.416227.4) (ISNI:0000 0004 0617 7616)
8 University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403); Leeds Teaching Hospitals NHS Trust, NIHR Leeds Biomedical Research Centre, Leeds, UK (GRID:grid.415967.8) (ISNI:0000 0000 9965 1030)
9 Royal College of Surgeons in Ireland, Department of Ophthalmology, Dublin 2, Ireland (GRID:grid.4912.e) (ISNI:0000 0004 0488 7120); Royal College of Surgeons in Ireland, School of Pharmacy and Biomolecular Sciences (PBS) and RSCI Research Institute, Dublin 2, Ireland (GRID:grid.4912.e) (ISNI:0000 0004 0488 7120)