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dc.contributor.authorThorlacius, Gudny Ella
dc.contributor.authorHultin-Rosenberg, Lina
dc.contributor.authorSandling, Johanna K.
dc.contributor.authorBianchi, Matteo
dc.contributor.authorImgenberg-Kreuz, Juliana
dc.contributor.authorTheander, Elke
dc.contributor.authorKvarnström, Marika
dc.contributor.authorForsblad-d’Elia, Helena
dc.contributor.authorBucher, Sara Magnusson
dc.contributor.authorNorheim, Katrine Brække
dc.contributor.authorJohnsen, Svein Joar Auglænd
dc.contributor.authorHammenfors, Sten Daniel
dc.contributor.authorSkarstein, Kathrine
dc.contributor.authorJonsson, Malin V
dc.contributor.authorBäcklund, Eva
dc.contributor.authorconsortium, the DISSECT
dc.contributor.authormeadows, jennifer r
dc.contributor.authorRantapää-Dahlqvist, Solbritt
dc.contributor.authorMandl, Thomas
dc.contributor.authorEriksson, Per
dc.contributor.authorOmdal, Roald
dc.contributor.authorJonsson, Sten Ture Roland
dc.contributor.authorLindblad-Toh, Kerstin
dc.contributor.authorRönnblom, Lars
dc.contributor.authorWahren-Herlenius, Marie
dc.contributor.authorNordmark, Gunnel
dc.description.abstractObjectives Clinical 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. Methods We 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. Results We 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. Conclusion Two 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.en_US
dc.publisherOxford University Pressen_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.titleGenetic and clinical basis for two distinct subtypes of primary Sjögren's syndromeen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCOpyright 2020 The Authorsen_US
dc.identifier.citationRheumatology. 2020, 60(2), 837–848en_US

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Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal