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Genetically Distinc...
Genetically Distinct Subsets within ANCA-Associated Vasculitis
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- Lyons, Paul A (författare)
- Addenbrookes Hospital, England
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- Rayner, Tim F (författare)
- Addenbrookes Hospital, England
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- Trivedi, Sapna (författare)
- Addenbrookes Hospital, England
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- Holle, Julia U (författare)
- University Hospital Schleswig Holstein, Germany
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- Watts, Richard A (författare)
- Ipswich Hospital National Health Serv Trust, England University of E Anglia, England
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- Jayne, David R W (författare)
- Addenbrookes Hospital, England University of Cambridge, England
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- Baslund, Bo (författare)
- Copenhagen University Hospital, Denmark
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- Brenchley, Paul (författare)
- University of Manchester, England
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- Bruchfeld, Annette (författare)
- Karolinska Institutet,Karolinska University Hospital, Sweden
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- Chaudhry, Afzal N (författare)
- Addenbrookes Hospital, England University of Cambridge, England
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- Tervaert, Jan Willem Cohen (författare)
- Maastricht University, Netherlands
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- Deloukas, Panos (författare)
- Wellcome Trust Sanger Institute, England
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- Feighery, Conleth (författare)
- Trinity Coll Dublin, Ireland St James Hospital, Ireland
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- Gross, Wolfgang L (författare)
- University Hospital Schleswig Holstein, Germany Klinikum Bad Bramstedt, Germany
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- Guillevin, Loic (författare)
- University of Paris, France
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- Gunnarsson, Iva (författare)
- Karolinska Institutet,Karolinska University Hospital, Sweden
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- Harper, Lorraine (författare)
- University of Birmingham, England
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- Hruskova, Zdenka (författare)
- Charles University of Prague, Czech Republic Gen University Hospital, Czech Republic
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- Little, Mark A (författare)
- UCL, England
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- Martorana, Davide (författare)
- University Hospital, Italy
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- Neumann, Thomas (författare)
- University Hospital, Germany
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- Ohlsson, Sophie (författare)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Karolinska Institute, Sweden Lund University, Sweden
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- Padmanabhan, Sandosh (författare)
- University of Glasgow, Scotland
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- Pusey, Charles D (författare)
- University of London Imperial Coll Science Technology and Med, England
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- Salama, Alan D (författare)
- UCL, England University of London Imperial Coll Science Technology and Med, England
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- Sanders, Jan-Stephan F (författare)
- University of Groningen, Netherlands
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- Savage, Caroline O (författare)
- GlaxoSmithKline, England
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- Segelmark, Mårten (författare)
- Lund University,Lunds universitet,Linköpings universitet,Farmakologi,Hälsouniversitetet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Stegeman, Coen A (författare)
- University of Birmingham, England University of Groningen, Netherlands
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- Tesar, Vladimir (författare)
- Charles University of Prague, Czech Republic Gen University Hospital, Czech Republic
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- Vaglio, Augusto (författare)
- University Hospital, Italy
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- Wieczorek, Stefan (författare)
- Ruhr University of Bochum, Germany
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- Wilde, Benjamin (författare)
- Maastricht University, Netherlands
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- Zwerina, Jochen (författare)
- University of Erlangen Nurnberg, Germany Medical University of Vienna, Austria Medical University of Vienna, Austria
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- Rees, Andrew J (författare)
- Medical University of Vienna, Austria
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- Clayton, David G (författare)
- Addenbrookes Hospital, England
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- Smith, Kenneth G C (författare)
- Addenbrookes Hospital, England
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(creator_code:org_t)
- Massachusetts Medical Society, 2012
- 2012
- Engelska.
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:3, s. 214-223
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND less thanbrgreater than less thanbrgreater thanAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegeners granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanA genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanWe found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanThis study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Lyons, Paul A
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Rayner, Tim F
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Trivedi, Sapna
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Holle, Julia U
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Watts, Richard A
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Jayne, David R W
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Baslund, Bo
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Brenchley, Paul
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Bruchfeld, Annet ...
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Chaudhry, Afzal ...
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Tervaert, Jan Wi ...
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Deloukas, Panos
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Feighery, Conlet ...
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Gross, Wolfgang ...
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Guillevin, Loic
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Gunnarsson, Iva
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Harper, Lorraine
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Hruskova, Zdenka
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Little, Mark A
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Martorana, David ...
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Neumann, Thomas
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Ohlsson, Sophie
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Padmanabhan, San ...
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Pusey, Charles D
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Salama, Alan D
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Sanders, Jan-Ste ...
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Savage, Caroline ...
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Segelmark, Mårte ...
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Stegeman, Coen A
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Tesar, Vladimir
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Vaglio, Augusto
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Wieczorek, Stefa ...
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Wilde, Benjamin
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Zwerina, Jochen
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Rees, Andrew J
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Clayton, David G
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Smith, Kenneth G ...
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Linköpings universitet
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Lunds universitet
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Karolinska Institutet