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Natural killer cell...
Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block
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- Ivanchenko, M (author)
- Karolinska Institutet
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- Thorlacius, GE (author)
- Karolinska Institutet
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- Hedlund, M (author)
- Karolinska Institutet
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- Ottosson, V (author)
- Karolinska Institutet
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- Meneghel, L (author)
- Karolinska Institutet
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Bjorkander, S (author)
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Ossoinak, A (author)
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- Tingstrom, J (author)
- Karolinska Institutet
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- Bremme, K (author)
- Karolinska Institutet
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Sverremark-Ekstrom, E (author)
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- Gemzell-Danielsson, K (author)
- Karolinska Institutet
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- Sonesson, SE (author)
- Karolinska Institutet
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- Chemin, K (author)
- Karolinska Institutet
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- Wahren-Herlenius, M (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-10-01
- 2021
- English.
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:2, s. 194-202
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Abstract
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- Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations.MethodsIn total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma.ResultsSimilar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hiNK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+and CD4+T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma.ConclusionOur study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
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- By the author/editor
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Ivanchenko, M
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Thorlacius, GE
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Hedlund, M
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Ottosson, V
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Meneghel, L
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Bjorkander, S
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show more...
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Ossoinak, A
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Tingstrom, J
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Bremme, K
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Sverremark-Ekstr ...
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Gemzell-Danielss ...
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Sonesson, SE
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Chemin, K
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Wahren-Herlenius ...
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- Articles in the publication
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Annals of the rh ...
- By the university
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Karolinska Institutet