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CD158a+ /CD158b+ NK cell imbalance correlates with hypertension in patients with pre-eclampsia
Xiuxiu Xu1,2, Xirui Zhao3, Ling Chen3
1Institute of Gerontology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China.
Insights
Peripheral natural killer (NK) cells, specifically CD158a+, increase while CD158b+ NK cells decrease in preeclampsia patients. This shift in NK cell populations correlates with elevated blood pressure in preeclampsia.
Area of Science:
- Immunology
- Obstetrics
- Genetics
Background:
- Preeclampsia is a serious pregnancy complication characterized by hypertension and proteinuria, with its underlying causes still not fully understood.
- The specific role of peripheral natural killer (NK) cells in the development of preeclampsia remains unclear, necessitating further investigation.
Purpose of the Study:
- To investigate the differential expression of CD158a and CD158b receptors on peripheral NK cells in women with preeclampsia compared to healthy pregnant women.
- To identify gene expression and protein alterations associated with these NK cell subsets in preeclampsia.
Main Methods:
- Flow cytometry was used to quantify CD158a (KIR2DL1) and CD158b (KIR2DL2/3) expression on peripheral NK cells.
- RNA-sequencing and real-time PCR were employed to analyze differentially expressed genes in CD158a+ and CD158b+ NK cells.
- Protein array analysis assessed serum protein levels in study participants.
Main Results:
- Patients with preeclampsia showed increased CD158a+ NK cells and decreased CD158b+ NK cells in peripheral blood.
- The proportion of CD158a+ NK cells positively correlated with systolic blood pressure, while CD158b+ NK cells showed a negative correlation.
- Gene expression analysis revealed decreased levels of ERAP2 and GCH1 in CD158a+ NK cells, impacting blood pressure regulation and angiogenesis. Serum protein levels related to angiogenesis were also altered.
Conclusions:
- A significant shift in peripheral NK cell populations, with an increase in CD158a+ and a decrease in CD158b+ cells, is observed in preeclampsia.
- These alterations in NK cell subsets are linked to the elevated blood pressure characteristic of preeclampsia, suggesting a potential role in disease pathogenesis.
Problem:
Preeclampsia, a pregnancy complication with hypertension and proteinuria, seriously threats the health and lives of the mother and the baby. The pathogenesis of pre-eclampsia remains incompletely understood. The role of peripheral natural killer cells (NK cells) in the pre-eclampsia is unclear.
Method Of Study:
Flow cytometry was performed to detect the expression of CD158a (KIR2DL1) and CD158b (KIR2DL2/3) in peripheral NK cells of healthy pregnant women (HP) and patients with pre-eclampsia (PE). Differentially expressed genes (DEGs) in CD158a+ and CD158b+ NK cells were identified by RNA-sequencing and real-time PCR. Protein array analysis was used to identify altered protein levels in the serum of study participants.
Results:
CD158a+ NK cell numbers were increased in the peripheral blood of patients while the number of CD158b+ NK cells was reduced. In addition, the percentage of CD158a+ NK cells within the peripheral NK subset was positively correlated with systolic blood pressure while the percentage of CD158b+ NK cells was negatively correlated with systolic blood pressure. RNA-seq and real-time PCR showed that the expression of ERAP2 and GCH1, the genes that regulate blood pressure and angiogenesis, was decreased in CD158a+ compared to CD158b+ NK cells. Consistently, the level of proteins involved in angiogenesis was altered in the serum of pre-eclampsia patients compared to healthy individuals.
Conclusions:
CD158a+ NK cells increased while CD158b+ NK cells decreased in the peripheral blood of patients with pre-eclampsia compared to healthy individuals. The change in the frequency of CD158a+ /CD158b+ NK cells is related to the increase in blood pressure.
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