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Genetic and clinica...
Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
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- Thorlacius, Guðný Ella (författare)
- Karolinska Institutet,Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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- Hultin-Rosenberg, Lina (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden,Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden
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- Sandling, Johanna K. (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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- Bianchi, Matteo (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Reumatologi,Uppsala Univ, Sweden; Uppsala Univ, Sweden; Uppsala Univ, Sweden,Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden; Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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- Imgenberg-Kreuz, Juliana (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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- Pucholt, Pascal, Dr, 1985- (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Univ Manchester, England,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden,Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom
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- Theander, Elke (författare)
- Skane Univ Hosp, Sweden,Department of Rheumatology, Skåne University Hospital, Malmö, Sweden
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- Kvarnström, Marika (författare)
- Karolinska Institutet,Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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- Forsblad d'Elia, Helena, 1961 (författare)
- Umeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Avdelningen för medicin
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- Magnusson Bucher, Sara (författare)
- Orebro Univ, Sweden,Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Sweden
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- Norheim, Katrine B. (författare)
- Stavanger Univ Hosp, Norway,Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
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- Auglænd Johnsen, Svein Joar (författare)
- Stavanger Univ Hosp, Norway,Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
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- Hammenfors, Daniel (författare)
- Haukeland Hosp, Norway,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
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- Skarstein, Kathrine (författare)
- Univ Bergen, Norway; Univ Bergen, Norway,Department of Clinical Science and Department of Clinical Dentistry, University of Bergen, Bergen, Norway
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- Jonsson, Malin V. (författare)
- Univ Bergen, Norway; Univ Bergen, Norway,Department of Clinical Science and Department of Clinical Dentistry, University of Bergen, Bergen, Norway
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- Baecklund, Eva, 1956- (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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- Aqrawi, Lara A. (författare)
- Univ Oslo, Norway,Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway
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- Liaaen Jensen, Janicke (författare)
- Univ Oslo, Norway,Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway
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- Palm, Øyvind (författare)
- Oslo Univ Hosp, Norway,Department of Rheumatology, Oslo University Hospital, Oslo, Norway
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Morris, Andrew P. (författare)
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- Meadows, Jennifer R. S. (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden,Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden
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- Rantapää-Dahlqvist, Solbritt (författare)
- Umeå universitet,Avdelningen för medicin
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- Mandl, Thomas (författare)
- Skane Univ Hosp, Sweden,Department of Rheumatology, Skåne University Hospital, Malmö, Sweden
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- Eriksson, Per (författare)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland,Department of Clinical and Experimental Medicine, Rheumatology/Division of Neuro and Inflammation Sciences, Linköping University, Linköping, Sweden
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- Lind, Lars (författare)
- Uppsala universitet,Klinisk epidemiologi,Uppsala Univ, Sweden,Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden
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- Omdal, Roald (författare)
- Stavanger Univ Hosp, Norway; Univ Bergen, Norway,Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
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- Jonsson, Roland (författare)
- Haukeland Hosp, Norway; Univ Bergen, Norway,Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway
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- Lindblad-Toh, Kerstin (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden; Broad Institute of MIT and Harvard, MA, Cambridge, United States,Uppsala Univ, Sweden; Broad Inst MIT & Harvard, MA 02142 USA
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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- Wahren-Herlenius, Marie (författare)
- Karolinska Institutet,Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden,Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Rheumatology, Uppsala, Sweden
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Palm, O (författare)
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- Andersson, Göran (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics
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(creator_code:org_t)
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- 2020
- 2021
- Engelska.
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
- Relaterad länk:
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https://doi.org/10.1...
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https://academic.oup...
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https://uu.diva-port... (primary) (Raw object)
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://gup.ub.gu.se...
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https://res.slu.se/i...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Sjögren's syndrome
- autoantibodies
- autoimmunity
- gene polymorphism
- Medicinsk vetenskap
- Medical Science
Publikations- och innehållstyp
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Thorlacius, Guðn ...
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Hultin-Rosenberg ...
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Sandling, Johann ...
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Bianchi, Matteo
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Imgenberg-Kreuz, ...
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Pucholt, Pascal, ...
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visa fler...
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Theander, Elke
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Kvarnström, Mari ...
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Forsblad d'Elia, ...
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Magnusson Bucher ...
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Norheim, Katrine ...
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Auglænd Johnsen, ...
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Hammenfors, Dani ...
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Skarstein, Kathr ...
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Jonsson, Malin V ...
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Baecklund, Eva, ...
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Aqrawi, Lara A.
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Liaaen Jensen, J ...
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Palm, Øyvind
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Morris, Andrew P ...
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Meadows, Jennife ...
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Rantapää-Dahlqvi ...
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Mandl, Thomas
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Eriksson, Per
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Lind, Lars
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Omdal, Roald
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Jonsson, Roland
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Lindblad-Toh, Ke ...
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Rönnblom, Lars
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Wahren-Herlenius ...
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Nordmark, Gunnel
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Palm, O
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Andersson, Göran
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
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Rheumatology
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Umeå universitet