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Type I IFN system a...
Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero
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- Hedlund, Malin (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Thorlacius, Gudny Ella (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Ivanchenko, Margarita (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Ottosson, Vijole (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Kyriakidis, Nikolaos (author)
- Karolinska Institute,Karolinska University Hospital,Universidad de Las Américas de Ecuador
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- Lagnefeldt, Linda (author)
- Karolinska Institute,Karolinska University Hospital
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- Tingström, Joanna (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Sirsjö, Allan, 1959- (author)
- Örebro University,Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre
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- Bengtsson, Anders A. (author)
- Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Aronsson, Emma (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Gemzell-Danielsson, Kristina (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Rönnblom, Lars (author)
- Uppsala University,Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Rheumatology, Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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- Bergman, Gunnar (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Espinosa, Alexander (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Sonesson, Sven-Erik (author)
- Karolinska Institute,Karolinska University Hospital
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- Eloranta, Maija-Leena (author)
- Uppsala University,Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Rheumatology, Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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- Wahren-Herlenius, Marie (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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(creator_code:org_t)
- 2020-01-07
- 2020
- English.
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In: RMD Open. - : BMJ. - 2056-5933. ; 6:1
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Abstract
Subject headings
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- OBJECTIVE: In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment.METHODS: Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays.RESULTS: We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14+ monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma.CONCLUSIONS: Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Sjøgren's syndrome
- autoantibodies
- autoimmune diseases
- Medicinsk vetenskap
- Medical Science
- autoantibodies
- autoimmune diseases
- Sjøgren's syndrome
Publication and Content Type
- ref (subject category)
- art (subject category)
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Hedlund, Malin
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Thorlacius, Gudn ...
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Ivanchenko, Marg ...
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Ottosson, Vijole
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Kyriakidis, Niko ...
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Lagnefeldt, Lind ...
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Tingström, Joann ...
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Sirsjö, Allan, 1 ...
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Bengtsson, Ander ...
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Aronsson, Emma
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Gemzell-Danielss ...
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Rönnblom, Lars
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Bergman, Gunnar
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Espinosa, Alexan ...
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Sonesson, Sven-E ...
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Eloranta, Maija- ...
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Wahren-Herlenius ...
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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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RMD Open
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Uppsala University
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Örebro University
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Lund University
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Karolinska Institutet