Type i IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero
(2020) In RMD Open 6(1).- 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,... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- autoantibodies, autoimmune diseases, Sjøgren's syndrome
- in
- RMD Open
- volume
- 6
- issue
- 1
- article number
- e000989
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85078525894
- pmid:31958275
- ISSN
- 2056-5933
- DOI
- 10.1136/rmdopen-2019-000989
- language
- English
- LU publication?
- yes
- id
- c23497ee-a369-4754-8556-012137369e98
- date added to LUP
- 2020-02-10 08:11:43
- date last changed
- 2024-06-13 11:31:02
@article{c23497ee-a369-4754-8556-012137369e98,
abstract = {{<p>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.</p>}},
author = {{Hedlund, Malin and Thorlacius, Gudny Ella and Ivanchenko, Margarita and Ottosson, Vijole and Kyriakidis, Nikolaos and Lagnefeldt, Linda and Tingström, Joanna and Sirsjö, Allan and Bengtsson, Anders A. and Aronsson, Emma and Gemzell-Danielsson, Kristina and Ronnblom, Lars and Bergman, Gunnar and Espinosa, Alexander and Sonesson, Sven Erik and Eloranta, Maija Leena and Wahren-Herlenius, Marie}},
issn = {{2056-5933}},
keywords = {{autoantibodies; autoimmune diseases; Sjøgren's syndrome}},
language = {{eng}},
number = {{1}},
publisher = {{BMJ Publishing Group}},
series = {{RMD Open}},
title = {{Type i IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero}},
url = {{http://dx.doi.org/10.1136/rmdopen-2019-000989}},
doi = {{10.1136/rmdopen-2019-000989}},
volume = {{6}},
year = {{2020}},
}