Search: onr:"swepub:oai:DiVA.org:uu-330755" >
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Li, HeOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA; University of Calif San Diego, CA 92093 USA
(author)
Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-06-22
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PUBLIC LIBRARY SCIENCE,2017
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-330755
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330755URI
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https://doi.org/10.1371/journal.pgen.1006820DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136143637URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-139633URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|NIH [P50AR0608040, 1R01AR065953, 5R01DE015223, 5RC2AR058959, 5P01AR049084, 5P30AR053483, 5U19AI082714, U19AI056363, 1R01DE018209, 5R01DE018209, 8P20GM103456, 1P30GM110766, 1R03AR065786, 5R37AI024717, 5P01AI083194, 7S10RR027190-02, 1U01AI101934, U54GM104938, S10RR026735, 5P30GM103510]; National Institute of Dental and Craniofacial Research; US Department of Veterans Affairs IM MA 9; USA Department of Defense [PR094002]; American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Preceptorship Award; Oklahoma Medical Research Foundation; Sjogrens Syndrome Foundation; Phileona Foundation; French ministry of health: PHRC [2006-AOM06133]; French ministry of research [ANR-2010-BLAN-1133]
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Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Reksten, Tove RagnaOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Bergen, Norway
(author)
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Ice, John A.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Kelly, Jennifer A.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Adrianto, IndraOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Rasmussen, AstridOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Wang, ShaofengOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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He, BoOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA
(author)
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Grundahl, Kiely M.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Glenn, Stuart B.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Miceli-Richard, CorinneUniv Paris Sud, Hop Univ Paris Sud, AP HP, INSERM,U1012, Le Kremlin Bicetre, France.,University of Paris Sud, France
(author)
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Bowman, SimonUniv Hosp Birmingham, Rheumatol Dept, Birmingham, W Midlands, England.,University Hospital Birmingham, England
(author)
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Lester, SueQueen Elizabeth Hosp, Adelaide, SA, Australia.,Queen Elizabeth Hospital, Australia
(author)
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Eriksson, Per,1958-Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)perer22
(author)
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Eloranta, Maija-LeenaUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)maelo020
(author)
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Brun, Johan G.Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway.,University of Bergen, Norway; Haukeland Hospital, Norway
(author)
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Goransson, Lasse G.Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.,Stavanger University Hospital, Norway
(author)
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Harboe, ErnaStavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.,Stavanger University Hospital, Norway
(author)
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Guthridge, Joel M.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Kaufman, Kenneth M.Cincinnati Childrens Hosp Med Ctr, Div Rheurnatol, Cincinnati, OH 45229 USA.;US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.,Cincinnati Childrens Hospital Medical Centre, OH 45229 USA; US Department Vet Affairs, OH USA
(author)
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Kvarnstrom, MarikaKarolinska Institutet,Karolinska Inst, Dept Med, Stockholm, Sweden.,Karolinska Institute, Sweden
(author)
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Graham, Deborah S. CunninghameKings Coll London, Dept Med & Mol Genet, London, England.
(author)
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Patel, KetanUniv Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA.;North Mem Med Ctr, Dept Oral & Maxillofacial Surg, Robbinsdale, MN USA.,University of Minnesota, MN 55455 USA; North Mem Medical Centre, MN USA
(author)
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Adler, Adam J.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA; University of Oklahoma, OK USA
(author)
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Farris, A. DariseOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA
(author)
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Brennan, Michael T.Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA.,Carolinas Medical Centre, NC 28203 USA
(author)
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Chodosh, JamesHarvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.,Harvard Medical Sch, MA USA
(author)
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Gopalakrishnan, RajaramUniv Minnesota, Sch Dent, Dept Diagnost & Biol Sci, Div Oral Pathol, Minneapolis, MN 55455 USA.,University of Minnesota, MN 55455 USA
(author)
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Weisman, Michael H.Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.,Cedars Sinai Medical Centre, CA 90048 USA
(author)
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Venuturupalli, SwamyCedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.,Cedars Sinai Medical Centre, CA 90048 USA
(author)
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Wallace, Daniel J.Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.,Cedars Sinai Medical Centre, CA 90048 USA
(author)
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Hefner, Kimberly S.Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.;Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA.,Cedars Sinai Medical Centre, CA 90048 USA; Hefner Eye Care and Opt Centre, OK USA
(author)
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Houston, Glen D.Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA.;Heartland Pathol Consultants, Edmond, OK USA.,University of Oklahoma, OK USA; Heartland Pathol Consultants, OK USA
(author)
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Huang, Andrew J. W.Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA.,Washington University, MO 63130 USA
(author)
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Hughes, Pamela J.Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA.,University of Minnesota, MN 55455 USA
(author)
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Lewis, David M.Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA.,University of Oklahoma, OK USA
(author)
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Radfar, LidaUniv Oklahoma, Coll Dent, Oral Diagnosis & Radiol Dept, Oklahoma City, OK USA.,University of Oklahoma, OK USA
(author)
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Vista, Evan S.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Santo Tomas Hosp, Manila, Philippines.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Santo Tomas Hospital, Philippines
(author)
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Edgar, Contessa E.Oklahoma Baptist Univ, Biol Dept, Oklahoma City, OK USA.,Oklahoma Baptist University, OK USA
(author)
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Rohrer, Michael D.Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA.,University of Minnesota, MN 55455 USA
(author)
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Stone, Donald U.Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.,Johns Hopkins University, MD USA
(author)
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Vyse, Timothy J.Kings Coll London, Dept Med & Mol Genet, London, England.
(author)
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Harley, John B.Cincinnati Childrens Hosp Med Ctr, Div Rheurnatol, Cincinnati, OH 45229 USA.;US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.,Cincinnati Childrens Hospital Medical Centre, OH 45229 USA; US Department Vet Affairs, OH USA
(author)
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Gaffney, Patrick M.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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James, Judith A.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
(author)
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Turner, SeanOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Alevizos, IliasNatl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.,National Institute Dent and Craniofacial Research, MD USA
(author)
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Anaya, Juan-ManuelUniv Rosario, Cente Autoimmune Dis Res, Bogota, Colombia.,University of Rosario, Colombia
(author)
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Rhodus, Nelson L.Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA.,University of Minnesota, MN 55455 USA
(author)
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Segal, Barbara M.Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA.,University of Minnesota, MN 55455 USA
(author)
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Montgomery, Courtney G.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Scofield, R. HalOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.;US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA; US Department Vet Affairs, OK USA
(author)
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Kovats, SusanOklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.,Oklahoma Medical Research Fdn, OK 73104 USA
(author)
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Mariette, XavierUniv Paris Sud, Hop Univ Paris Sud, AP HP, INSERM,U1012, Le Kremlin Bicetre, France.,University of Paris Sud, France
(author)
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Rönnblom, LarsUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)larsronn
(author)
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Witte, TorstenHannover Med Sch, Clin Immunol & Rheumatol, Hannover, Germany.,Hannover Medical Sch, Germany
(author)
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Rischmueller, MaureenQueen Elizabeth Hosp, Adelaide, SA, Australia.;Univ Adelaide, Adelaide, SA, Australia.,Queen Elizabeth Hospital, Australia; University of Adelaide, Australia
(author)
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Wahren-Herlenius, MarieKarolinska Institutet,Karolinska Inst, Dept Med, Stockholm, Sweden.,Karolinska Institute, Sweden
(author)
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Omdal, RoaldStavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.,Stavanger University Hospital, Norway
(author)
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Jonsson, RolandUniv Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.;Haukeland Hosp, Dept Rheumatol, Bergen, Norway.,University of Bergen, Norway; Haukeland Hospital, Norway
(author)
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Ng, Wan-FaiNewcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.;Newcastle Univ, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England.,Newcastle University, England; Newcastle University, England
(author)
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Nordmark, GunnelUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)gunnnord
(author)
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Lessard, Christopher J.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA
(author)
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Sivils, Kathy L.Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.,Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA
(author)
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Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.;Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.Oklahoma Medical Research Fdn, OK 73104 USA; University of Oklahoma, OK USA; University of Calif San Diego, CA 92093 USA
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Radfar, Lida
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Vista, Evan S.
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Stone, Donald U.
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James, Judith A.
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Turner, Sean
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Alevizos, Ilias
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Segal, Barbara M ...
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Montgomery, Cour ...
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Scofield, R. Hal
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Kovats, Susan
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Mariette, Xavier
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Rönnblom, Lars
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Witte, Torsten
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Rischmueller, Ma ...
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Wahren-Herlenius ...
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Omdal, Roald
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Ng, Wan-Fai
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