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Complement C4 Copy ...
Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases
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- Lundtoft, Christian (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Pucholt, Pascal, Dr, 1985- (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Martin, Myriam (author)
- Karolinska Institutet,Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,Lund Univ, Sweden
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- Bianchi, Matteo (author)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Sci Life Lab, Sweden
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- Lundstrom, Emeli (author)
- Karolinska Institute,Karolinska University Hospital,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Eloranta, Maija-Leena (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Sandling, Johanna K. (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Sjöwall, Christopher (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland,Linköping University, Linköping, Sweden,Linköping Univ, Linköping, Sweden
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- Jönsen, Andreas (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital,Lund Univ, Sweden; Skane Univ Hosp, Sweden
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- Gunnarsson, Iva (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Rantapää-Dahlqvist, Solbritt (author)
- Umeå University,Umeå universitet,Reumatologi,Umeå Univ, Umeå, Sweden
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- Bengtsson, Anders A. (author)
- Lund Univ, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden,Lund University and Skåne University Hospital, Lund, Sweden
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- Leonard, Dag, 1975- (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Baecklund, Eva, 1956- (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Jonsson, Roland (author)
- Univ Bergen, Bergen, Norway,University of Bergen, Bergen, Norway
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- Hammenfors, Daniel (author)
- Haukeland Hosp, Bergen, Norway,Haukeland University Hospital, Bergen, Norway
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- Forsblad d'Elia, Helena, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Eriksson, Per (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland,Linköping University, Linköping, Sweden,Linköping Univ, Linköping, Sweden
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- Mandl, Thomas (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Reumatologi,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Rheumatology,Lund University Research Groups,Lund Univ, Sweden
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- Bucher, Sara Magnusson (author)
- Örebro University,Orebro Univ, Sweden
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- Norheim, Katrine B. (author)
- Stavanger Univ Hosp, Stavanger, Norway,Stavanger University Hospital, Stavanger, Norway
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- Johnsen, Svein Joar Auglaend (author)
- Stavanger Univ Hosp, Stavanger, Norway,Stavanger University Hospital, Stavanger, Norway
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- Omdal, Roald (author)
- Stavanger Univ Hosp, Stavanger, Norway,Stavanger University Hospital, Stavanger, Norway
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- Kvarnstrom, Marika (author)
- Karolinska Institute,Stockholm Regional Council,Karolinska University Hospital,Karolinska Univ Hosp, Sweden; Reg Stockholm, Sweden
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- Wahren-Herlenius, Marie (author)
- Karolinska Institute,Karolinska University Hospital,University of Bergen,Univ Bergen, Norway; Karolinska Inst, Sweden; Karolinska Univ Hosp Stockholm, Sweden
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- Notarnicola, Antonella (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Andersson, Helena (author)
- Oslo Univ Hosp, Oslo, Norway,Oslo University Hospital, Oslo, Norway
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- Molberg, Oyvind (author)
- Oslo Univ Hosp, Oslo, Norway,Oslo University Hospital, Oslo, Norway
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- Diederichsen, Louise Pyndt (author)
- Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.;Odense Univ Hosp, Odense, Denmark,Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, and Odense University Hospital, Odense, Denmark
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- Almlöf, Jonas (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Sweden; Sci Life Lab, Sweden
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- Syvänen, Ann-Christine, 1950- (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin,Uppsala Univ, Sweden; Sci Life Lab, Sweden
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- Kozyrev, Sergey V. (author)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Sci Life Lab, Sweden
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- Lindblad-Toh, Kerstin (author)
- Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA,Massachusetts Institute of Technology,Uppsala Univ, Sweden; Sci Life Lab, Sweden; Broad Inst MIT & Harvard, MA 02142 USA
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- Nilsson, Bo (author)
- Uppsala universitet,Vaskulärbiologi,Uppsala Univ, Sweden
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- Blom, Anna M. (author)
- Lund Univ, Sweden
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- Lundberg, Ingrid E. (author)
- Karolinska Institutet
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- Nordmark, Gunnel (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Diaz-Gallo, Lina Marcela (author)
- Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden,Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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- Svenungsson, Elisabet (author)
- Karolinska Institutet
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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(creator_code:org_t)
- 2022-06-27
- 2022
- English.
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:8, s. 1440-1450
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Abstract
Subject headings
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- Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Lundtoft, Christ ...
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Pucholt, Pascal, ...
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Martin, Myriam
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Bianchi, Matteo
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Lundstrom, Emeli
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Eloranta, Maija- ...
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show more...
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Sandling, Johann ...
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Sjöwall, Christo ...
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Jönsen, Andreas
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Gunnarsson, Iva
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Rantapää-Dahlqvi ...
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Bengtsson, Ander ...
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Leonard, Dag, 19 ...
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Baecklund, Eva, ...
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Jonsson, Roland
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Hammenfors, Dani ...
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Forsblad d'Elia, ...
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Eriksson, Per
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Mandl, Thomas
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Bucher, Sara Mag ...
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Norheim, Katrine ...
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Johnsen, Svein J ...
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Omdal, Roald
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Kvarnstrom, Mari ...
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Wahren-Herlenius ...
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Notarnicola, Ant ...
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Andersson, Helen ...
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Molberg, Oyvind
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Diederichsen, Lo ...
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Almlöf, Jonas
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Syvänen, Ann-Chr ...
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Kozyrev, Sergey ...
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Lindblad-Toh, Ke ...
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Nilsson, Bo
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Blom, Anna M.
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Lundberg, Ingrid ...
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Nordmark, Gunnel
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Diaz-Gallo, Lina ...
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Svenungsson, Eli ...
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Rönnblom, Lars
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Arthritis & Rheu ...
- By the university
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Linköping University
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Umeå University
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Uppsala University
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Lund University
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Karolinska Institutet
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University of Gothenburg