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01.15 Type I IFN system activation in newborns exposed to anti-ro/ssa autoantibodies in utero
  1. Malin Hedlund1,
  2. Gudny Ella Thorlacius1,
  3. Margarita Ivanchenko1,
  4. Nikolaos Kyriakidis1,
  5. Lars Rönnblom2,
  6. Maija-Lena Eloranta2,
  7. Alexander Espinosa1,
  8. Sven-Erik Sonesson3,
  9. Marie Wahren-Herlenius1
  1. 1Experimental Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  2. 2Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  3. 3Paediatric Cardiology Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Abstract

Background Overexpression of type I IFN-stimulated genes has been demonstrated in both SLE and SS, and induction of IFNα production in plasmacytoid dendritic cells by immune complexes containing RNA and autoantibodies, including Ro/SSA and La/SSB autoantibodies, has also been shown. During pregnancy, these autoantibodies pass over the placenta to the fetus, but it is not know if an IFN-activation takes place also in the fetus. In the present study, we therefore investigated if the type I IFN system is activated in newborns exposed to anti-Ro/SSA autoantibodies in utero.

Materials and methods Anti-Ro/SSA positive mothers and their babies as well as healthy controls were included in the study. Maternal and cord blood drawn at birth was immediately separated into plasma and PBMC. mRNA expression was analysed by microarrays, cell surface markers were assessed by flow cytometry and circulating IFNα levels by DELFIA.

Results We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/SSA positive women but also in their newborns, with maternal and fetal IFN scores showing a significant positive correlation (r=0.74, p=0.005). Increased expression of MHC class II was observed on CD14+ monocytes of anti-Ro/SSA antibody-exposed babies, suggesting cellular activation. Notably, the IFN score of babies born to mothers receiving immunomodulatory treatment was similar to that of controls.

Conclusions We demonstrate for the first time that anti-Ro/SSA antibody-exposed babies at risk for neonatal lupus have a pre-activated immune system with an IFN signature, elevated plasma IFNα, and increased MHC class II expression on circulating monocytes. Our data also suggest that maternal immunomodulatory treatment may modulate the IFN activity in the baby.

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