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PBMC-derived RNA signatures show impaired ability to regulate immune responses in women developing preeclampsia
Monica Frøystad1,2, Thor Ueland1,2, Marie Cecilie Paasche Roland3
1Research Institute of Internal Medicine, Oslo University Hospital, Norway.
Insights
Preeclampsia involves altered immune responses, with specific RNA changes detected during and after pregnancy. Downregulated long non-coding RNAs correlate with markers of endothelial dysfunction and platelet activation in preeclampsia.
Area of Science:
- Immunology
- Genetics
- Maternal Health
Background:
- Preeclampsia is a pregnancy complication with unknown causes, hindering early detection.
- Understanding molecular changes in preeclampsia is crucial for improving outcomes.
Purpose of the Study:
- To investigate the roles of protein-coding and long non-coding (lnc) RNAs in preeclampsia development.
- To analyze RNA profiles in peripheral blood mononuclear cells (PBMCs) during and after pregnancy.
Main Methods:
- PBMCs were isolated from women with preeclampsia and normal pregnancies at multiple time points.
- RNA sequencing and quantitative PCR (qPCR) were performed.
- Bioinformatics and correlation analyses were used to examine RNA dysregulation and associations.
Main Results:
- Dysregulated RNAs were identified at all time points, predominantly at 36-38 weeks of gestation.
- Most downregulated RNAs were lncRNAs, correlating with preeclampsia markers like P-selectin and sFlt-1.
- Immune responses showed increased adaptive activation and dampened innate immunity, including Notch signaling alterations.
Conclusions:
- Circulating RNAs in preeclampsia suggest enhanced adaptive and dampened innate immune responses.
- Downregulated lncRNAs may indicate impaired immune regulation, linked to endothelial dysfunction and platelet activation.
- Further research into the function of circulating lncRNAs in preeclampsia is warranted.
Abstract:
Preeclampsia is a serious pregnancy complication with unclear etiology, making early detection challenging but imperative to improve prognosis. We here examine the potential roles of protein-coding and long non-coding (lnc) RNA from peripheral blood mononuclear cells (PBMCs) in the development of preeclampsia by examining women during pregnancy and 5 years following pregnancy. We isolated PBMCs from women with preeclampsia (N=37) and normal pregnant controls (N=215) at 22-24 and 36-38 weeks of gestation, and 5-year follow-up. We performed RNA sequencing at all time points for N=7 normal pregnant controls and N=9 women with preeclampsia and explored data manually and using bioinformatics analyses. Spearman correlation was used between lncRNA and preeclampsia-associated markers while Notch-related RNAs were measured by qPCR. We found dysregulated RNAs at all timepoints, mostly at 36-38 weeks (491 upregulated, 155 downregulated). Most downregulated RNAs were lncRNA and these correlated positively with P-selectin and negatively with sFlt-1 and myeloperoxidase from the maternal circulation. Overrepresentation analyses and manual data exploration at 36-38 weeks revealed increased activation of adaptive immune functions and dampening of innate immune response, including Notch signalling. NOTCH2NLA/B/C was decreased at 22-24 weeks in the total cohort. In conclusion, circulating protein-coding and lncRNA from women developing preeclampsia broadly indicate enhanced adaptive immune cell activation but dampened innate immune responses including impaired Notch-signalling. The association of downregulated lncRNAs with markers of endothelial dysfunction and platelet activation may support impaired immune regulation in these women. The function of circulating lncRNAs in women with preeclampsia warrants further study.
