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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Scientific reports - 11(2021), 1 vom: 15. Apr., Seite 8272 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Batten, Isabella [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.11.2021 Date Revised 22.11.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-021-87760-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324140363 |
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| 100 | 1 | |a Batten, Isabella |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Investigation of type I interferon responses in ANCA-associated vasculitis |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Robinson, Mark W |e verfasserin |4 aut | |
| 700 | 1 | |a White, Arthur |e verfasserin |4 aut | |
| 700 | 1 | |a Walsh, Cathal |e verfasserin |4 aut | |
| 700 | 1 | |a Fazekas, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Wyse, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Buettner, Antonia |e verfasserin |4 aut | |
| 700 | 1 | |a D'Arcy, Suzanne |e verfasserin |4 aut | |
| 700 | 1 | |a Greenan, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Conor C |e verfasserin |4 aut | |
| 700 | 1 | |a Wigston, Zoe |e verfasserin |4 aut | |
| 700 | 1 | |a Gabhann-Dromgoole, Joan Ní |e verfasserin |4 aut | |
| 700 | 1 | |a Vital, Edward M |e verfasserin |4 aut | |
| 700 | 1 | |a Little, Mark A |e verfasserin |4 aut | |
| 700 | 1 | |a Bourke, Nollaig M |e verfasserin |4 aut | |
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