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Genetically Distinc...
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Lyons, Paul AAddenbrookes Hospital, England
(författare)
Genetically Distinct Subsets within ANCA-Associated Vasculitis
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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Massachusetts Medical Society,2012
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-79637
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-79637URI
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https://doi.org/10.1056/NEJMoa1108735DOI
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https://lup.lub.lu.se/record/2991588URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:124949088URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies|British Heart Foundation|SP/09/001/27117|Wellcome Trust|083650/Z/07/Z|National Institute of Health Research Biomedical Research Centres of Cambridge, Imperial College, and Manchester||Medical Research Council||Kidney Research UK||West Anglia Comprehensive Local Research Network||Norfolk and Suffolk Comprehensive Local Research Network||German Research Foundation|KFO170|European Union|CP-FP 261382|
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Rayner, Tim FAddenbrookes Hospital, England
(författare)
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Trivedi, SapnaAddenbrookes Hospital, England
(författare)
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Holle, Julia UUniversity Hospital Schleswig Holstein, Germany
(författare)
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Watts, Richard AIpswich Hospital National Health Serv Trust, England University of E Anglia, England
(författare)
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Jayne, David R WAddenbrookes Hospital, England University of Cambridge, England
(författare)
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Baslund, BoCopenhagen University Hospital, Denmark
(författare)
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Brenchley, PaulUniversity of Manchester, England
(författare)
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Bruchfeld, AnnetteKarolinska Institutet,Karolinska University Hospital, Sweden
(författare)
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Chaudhry, Afzal NAddenbrookes Hospital, England University of Cambridge, England
(författare)
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Tervaert, Jan Willem CohenMaastricht University, Netherlands
(författare)
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Deloukas, PanosWellcome Trust Sanger Institute, England
(författare)
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Feighery, ConlethTrinity Coll Dublin, Ireland St James Hospital, Ireland
(författare)
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Gross, Wolfgang LUniversity Hospital Schleswig Holstein, Germany Klinikum Bad Bramstedt, Germany
(författare)
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Guillevin, LoicUniversity of Paris, France
(författare)
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Gunnarsson, IvaKarolinska Institutet,Karolinska University Hospital, Sweden
(författare)
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Harper, LorraineUniversity of Birmingham, England
(författare)
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Hruskova, ZdenkaCharles University of Prague, Czech Republic Gen University Hospital, Czech Republic
(författare)
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Little, Mark AUCL, England
(författare)
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Martorana, DavideUniversity Hospital, Italy
(författare)
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Neumann, ThomasUniversity Hospital, Germany
(författare)
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Ohlsson, SophieLund 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(Swepub:lu)njur-soh
(författare)
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Padmanabhan, SandoshUniversity of Glasgow, Scotland
(författare)
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Pusey, Charles DUniversity of London Imperial Coll Science Technology and Med, England
(författare)
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Salama, Alan DUCL, England University of London Imperial Coll Science Technology and Med, England
(författare)
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Sanders, Jan-Stephan FUniversity of Groningen, Netherlands
(författare)
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Savage, Caroline OGlaxoSmithKline, England
(författare)
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Segelmark, MårtenLund 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(Swepub:lu)njur-mse
(författare)
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Stegeman, Coen AUniversity of Birmingham, England University of Groningen, Netherlands
(författare)
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Tesar, VladimirCharles University of Prague, Czech Republic Gen University Hospital, Czech Republic
(författare)
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Vaglio, AugustoUniversity Hospital, Italy
(författare)
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Wieczorek, StefanRuhr University of Bochum, Germany
(författare)
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Wilde, BenjaminMaastricht University, Netherlands
(författare)
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Zwerina, JochenUniversity of Erlangen Nurnberg, Germany Medical University of Vienna, Austria Medical University of Vienna, Austria
(författare)
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Rees, Andrew JMedical University of Vienna, Austria
(författare)
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Clayton, David GAddenbrookes Hospital, England
(författare)
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Smith, Kenneth G CAddenbrookes Hospital, England
(författare)
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Addenbrookes Hospital, EnglandUniversity Hospital Schleswig Holstein, Germany
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:New England Journal of Medicine: Massachusetts Medical Society367:3, s. 214-2230028-47931533-4406
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Till lärosätets databas
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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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visa fler...
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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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