Genetically Distinct Subsets within ANCA-Associated Vasculitis

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Genetically Distinct Subsets within ANCA-Associated Vasculitis

Lyons, Paul A (författare): Addenbrookes Hospital, England

Rayner, Tim F (författare): Addenbrookes Hospital, England

Trivedi, Sapna (författare): Addenbrookes Hospital, England

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Holle, Julia U (författare): University Hospital Schleswig Holstein, Germany

Watts, Richard A (författare): Ipswich Hospital National Health Serv Trust, England University of E Anglia, England

Jayne, David R W (författare): Addenbrookes Hospital, England University of Cambridge, England

Baslund, Bo (författare): Copenhagen University Hospital, Denmark

Brenchley, Paul (författare): University of Manchester, England

Bruchfeld, Annette (författare): Karolinska Institutet,Karolinska University Hospital, Sweden

Chaudhry, Afzal N (författare): Addenbrookes Hospital, England University of Cambridge, England

Tervaert, Jan Willem Cohen (författare): Maastricht University, Netherlands

Deloukas, Panos (författare): Wellcome Trust Sanger Institute, England

Feighery, Conleth (författare): Trinity Coll Dublin, Ireland St James Hospital, Ireland

Gross, Wolfgang L (författare): University Hospital Schleswig Holstein, Germany Klinikum Bad Bramstedt, Germany

Guillevin, Loic (författare): University of Paris, France

Gunnarsson, Iva (författare): Karolinska Institutet,Karolinska University Hospital, Sweden

Harper, Lorraine (författare): University of Birmingham, England

Hruskova, Zdenka (författare): Charles University of Prague, Czech Republic Gen University Hospital, Czech Republic

Little, Mark A (författare): UCL, England

Martorana, Davide (författare): University Hospital, Italy

Neumann, Thomas (författare): University Hospital, Germany

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

Padmanabhan, Sandosh (författare): University of Glasgow, Scotland

Pusey, Charles D (författare): University of London Imperial Coll Science Technology and Med, England

Salama, Alan D (författare): UCL, England University of London Imperial Coll Science Technology and Med, England

Sanders, Jan-Stephan F (författare): University of Groningen, Netherlands

Savage, Caroline O (författare): GlaxoSmithKline, England

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

Stegeman, Coen A (författare): University of Birmingham, England University of Groningen, Netherlands

Tesar, Vladimir (författare): Charles University of Prague, Czech Republic Gen University Hospital, Czech Republic

Vaglio, Augusto (författare): University Hospital, Italy

Wieczorek, Stefan (författare): Ruhr University of Bochum, Germany

Wilde, Benjamin (författare): Maastricht University, Netherlands

Zwerina, Jochen (författare): University of Erlangen Nurnberg, Germany Medical University of Vienna, Austria Medical University of Vienna, Austria

Rees, Andrew J (författare): Medical University of Vienna, Austria

Clayton, David G (författare): Addenbrookes Hospital, England

Smith, Kenneth G C (författare): Addenbrookes Hospital, England

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(creator_code:org_t)

Massachusetts Medical Society, 2012
2012
Engelska.
Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:3, s. 214-223

Relaterad länk:: http://dx.doi.org/10...; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; http://kipublication...; visa färre...

Tidskriftsartikel (refereegranskat)

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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.)

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Genetically Distinct Subsets within ANCA-Associated Vasculitis

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