Type i IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Malin Hedlund
  • Gudny Ella Thorlacius
  • Margarita Ivanchenko
  • Vijole Ottosson
  • Nikolaos Kyriakidis
  • Linda Lagnefeldt
  • Joanna Tingström
  • Allan Sirsjö
  • Anders A. Bengtsson
  • Emma Aronsson
  • Kristina Gemzell-Danielsson
  • Lars Ronnblom
  • Gunnar Bergman
  • Alexander Espinosa
  • Sven Erik Sonesson
  • Maija Leena Eloranta
  • Marie Wahren-Herlenius
Organisations
External organisations
  • Karolinska University Hospital
  • Universidad de Las Américas de Ecuador
  • Örebro University
  • Uppsala University
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity

Keywords

  • autoantibodies, autoimmune diseases, Sjøgren's syndrome
Original languageEnglish
Article numbere000989
JournalRMD Open
Volume6
Issue number1
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes