Article Text
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.
- autoantibodies
- autoimmune diseases
- Sjøgren's syndrome
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Footnotes
MH and GET are joint first authors.
Contributors MH, GET and MW-H conceived the study. MH, GET, MI, VO, NK, LL, JT, AS, AAB, EA, KG, LR, GB, AE, S-ES, M-LE performed experiments, contributed to data acquisition and analysis. MH, GET and MW-H took the lead in writing the manuscript. All authors provided critical review and approval of the final version manuscript.
Funding This study was supported by grants from the Swedish Research Council, the Heart-Lung Foundation, the Stockholm County Council, the Karolinska Institute, the Swedish Rheumatism Association, King Gustaf the V:th 80-year Foundation, the Swedish Society of Medicine, the Ingegerd Johansson donation, the Foundation Samariten and the Torsten and Ragnar Söderberg Foundation.
Competing interests None declared.
Patient consent for publication The mothers gave written informed consent.
Ethics approval The study was approved by the Local Ethics Committee Stockholm.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.