Natural Killer Cells And Type Ii Interferon In Ro/Ssa And La/Ssb Autoantibody-Exposed Newborns At Risk Of Congenital Heart Block
ANNALS OF THE RHEUMATIC DISEASES(2021)
摘要
Objective 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.Methods In 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.Results Similar to non-pregnant systemic lupus erythematosus and Sjogren-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 CD56(dim)CD16(hi) NK 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 IFN. production by NK cells, CD8(+) and CD4(+) T cells in anti-Ro/La exposed neonates. IFN. was also detectable in their plasma.Conclusion Our 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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关键词
B cells,autoantibodies,autoimmunity,sjøgren's syndrome
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