Abnormal Pro-inflammatory Immune Cell Responses Precede Clinical Onset of Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are significant contributors to maternal morbidity and mortality, as well as to long-term cardiovascular health, with an inequitable burden among Black individuals. While there is growing interest in the possibility that inflammatory responses are involved with HDP, work to date has primarily been cross-sectional, and immune cell profiling has focused on cell phenotyping that may not capture relevant functional properties of the immune cells.

We examined whether an abnormal inflammatory cellular profile is found in the blood of Black pregnant women before the clinical onset of HDP. This nested case-control study included 27 pregnant women who later developed HDP and 73 who had a healthy pregnancy delivered at term, all of whom provided blood samples during the second trimester. Phenotype and function of immune cell populations were examined by multi-parametric flow cytometry.

We observed a greater abundance of peripheral blood T cells in individuals later diagnosed with HDP. Among these were CD161⁺ CD4 T cells that showed increased expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF). Similarly, monocytes from these individuals exhibited increased expression of pro-inflammatory cytokines. Anti-inflammatory T cells and monocytes were not altered in those with versus without a future diagnosis of HDP.

We identify a pro-inflammatory cellular immune signature in pregnant individuals destined to have HDP. Immune signatures may serve as a new biomarker to identify subsets of individuals at particular risk for HDP and point to new therapeutic targets to prevent HDP.