Borchers, Anna

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy defined by new-onset hypertension occurring after 20 weeks of pregnancy, with end organ damage. Pro-inflammatory changes are also observed in these patients. Although the clinical features of PE are resolved soon after delivery, affected patients face a higher risk and earlier onset of cardiovascular disease (CVD). It is unknown what leads to this persistent elevated risk, and long-term alterations of the maternal immune system could be involved. Study objective: Our goal was to address the immune alterations and functional changes in the first year postpartum in PE as compared to normotensive (NT) pregnancies. Hypothesis: We hypothesize that the maternal immune profile is altered in the postpartum period in PE vs NT patients, with a proinflammatory bias and altered function in PE patients. Brief Statement of Methods: We prospectively followed 31 women (PE=15, NT=16) and collected blood 24 hours, and 3, 6, and 12 months postpartum. Plasma and peripheral blood mononuclear cells (PBMC) were isolated and stored for analysis. Inflammatory mediators were quantified through multiplex assays, and PBMCs profile were defined through flow cytometry as well as following inflammatory stimuli to assess their functional changes through intracellular cytokine staining and expression of activation markers. Summary of Results: PE patients had elevated CD3+ T cell frequencies at 3 and 12 months postpartum compared to NT patients. Both groups showed reduced CD14+ monocytes across postpartum timepoints compared with 24 hours. PE was also associated with increased amounts of pro-inflammatory cytokines (such as IL1α, IL9, IFNγ), chemokines and growth factors at multiple timepoints throughout the first year postpartum; NT patients had decreased amounts of pro-inflammatory cytokines. Intracellular staining showed altered immune cell functions in PE, with decreased IL-6 production following polyI:C stimulation and decreased IL-10+ monocytes after LPS and polyI:C at 3 months postpartum. At 3 months, PE patients had increased markers of activation (i.e. CD69+) in both NK cells and T cells, the latter following PMA/Ionomycin stimulation. Statement of Conclusions: Pregnancy itself induces lasting immune changes persisting to 12 months postpartum, even in NT patients, whilst PE complicated pregnancies have sustained inflammation and altered immune function in the postpartum period. Overall, this work will provide essential insight into an understudied period that many women experience and help to identify long lasting immunological changes that could impact long term maternal health. Future work will explore the impact of this sustained inflammation on epigenetic modifications in immune cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Context.— The US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for SARS-CoV-2 assays encompassed both in vitro diagnostic and laboratory-developed tests. Related testing data and documents from EUAs were published on the FDA website as PDF files, constituting a rich data resource. Objective.— To highlight the value of structured descriptive and validation data and provide recommendations on improving the quality, accessibility, and shareability of the FDA’s digital resources. Design.— SARS-CoV-2 diagnostics EUAs and related files were acquired from the FDA, and data were extracted through an iterative manual or automated process with quality assurance in accordance with a set of data entry definitions to generate a data product (ie, data analysis and presentation of data into tables, graphs, and reports, optionally including different data sets) that could be disseminated. Results.— Four challenges limited the usability of FDA EUA data, including (1) distinguishing EUA tests owing to similar names or inconsistent naming conventions; (2) document location and tracking owing to inconsistent EUA document identifiers, resource locators, and versioning; (3) data location and retrieval owing to heterogeneous structure and data formatting within EUA documentation; and (4) maintenance of existing data owing to lack of clear and traceable communication around EUA amendments. Conclusions.— Converging efforts from disparate groups to extract and synthesize FDA test data reveal an unaddressed need for better organization and communication. Existing FDA data reporting systems must be improved and adapted for the demands of the connected data science era.

Abstract Description Hypertensive disorders of pregnancy (HDP) include preeclampsia (PE) and gestational hypertension (gHTN), both suspected to be immune-driven pathologies. Our data shows that both PE and gHTN involve systemic immune cell activation and increased proinflammatory cytokines however it is unclear how these immune profiles play a role in the pathogenesis of disease. We hypothesize that pregnancies complicated with HDP have dysregulated immune profiles, including hyperactive T cells which are activating the vascular endothelium. We have investigated the circulating immune profiles of patients with normotensive (NT), PE or gHTN pregnancies at the RNA, protein and cellular levels, which show significant alterations in T cells, among others. We have seen increased levels of IL-6, CXCL9 and CXCL10 in the plasma of HDP patients vs NT, suggesting the polarization and recruitment of T cells. Using cytometry by time of flight (CyTOF), we have seen changes in expression of CD11a and CXCR3 on CD4+, CD8+ and yd T cells in HDP compared to NT. Single cell RNA sequencing of CD4+ and CD8+ T cells from PE vs NT shows increased expression of genes related to pathways such as allograft rejection, angiogenesis and cytokine signaling. Our in vitro co-culture experiments examine the ability of immune cells, specifically T cells, to activate endothelial cells. These studies will address the functional contribution of T cells to endothelial activation, which is a hallmark of the hypertension seen in HDP. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

Abstract Description Innate lymphoid cells (ILCs) play a key role in the mucosal innate immune system, particularly in cytokine production. While studies in mice have shown that ILCs are involved in epithelial barrier maintenance and pathogen protection, their role in human mucosal immunity, especially in the female genital tract (FGT), has yet to be fully explored. Here, we characterized genital ILC subpopulations from human hysterectomy samples (endometrium, endocervix, and ectocervix) using spectral flow cytometry, CITE-seq, and ChipCytometry for spatial analysis, and assessed their response to HIV stimulation. Our results reveal novel compartmentalization of genital ILC subsets, with CD161 and NKp44 following opposite expression patterns that distinguish functional states both at steady-state and in response to HIV. At rest, CD161+ ILC3s were enriched for IL-22, and CD161- ILC1s for IFN-g. In contrast, NKp44 was linked to degranulation and identified ILC3s in lymphoid aggregates in the endometrium. Following HIV stimulation, genital ILCs mounted an antiviral response within 30 minutes via transcriptional changes. CD161 expression predicted cytokine secretion (IFN-g and IL-22) in preloaded ILCs and was downregulated after stimulation, while NKp44 was upregulated. These findings highlight the unique role of human genital ILCs in mucosal protection prior to and following viral stimulation. Funding Sources NIH R01AG060801 (MRG) R21AI172065 (MRG) U01AG084766 (MRG) Burroughs Welcome Fund PATH award (1334236) (MRG) Topic Categories Mucosal and Regional Immunology (MUC)

Abstract Pre-eclampsia (PE) affects 5–8% of pregnancies and has detrimental effects on maternal–fetal health. PE is characterized by de novo hypertension after 20 wk of gestation and end-organ damage. Systemic inflammatory imbalance has been associated with PE, but its contribution to the pathology is poorly understood. Our objective was to investigate maternal systemic immune changes in early-onset PE (EOPE) and late-onset PE (LOPE) versus uncomplicated pregnancies (control [CTRL]), and their contribution to endothelial activation, hallmark of hypertension. Blood samples were analyzed by flow cytometry, multiplex assay, intracellular cytokine staining, and single-cell RNA sequencing. We performed cocultures between circulating immune cells and HUVECs to assess endothelial activation. We found that EOPE had decreased regulatory T cells (4.64±0.33, p < 0.05) and monocytes (33.92±3.08, p < 0.01), whereas LOPE had decreased regulatory T cells (4.60±0.30, p < 0.05) and Th2 cells (7.50±0.62, p < 0.01) versus CTRL. Compared to CTRL, elevated cytokines/chemokines, and growth factors were observed in LOPE, whereas EOPE primarily showed decreased levels. Using intracellular cytokine staining, we observed more monocytes producing IL-12, TNF-α, and IL-1β (all p < 0.05) in LOPE versus CTRL. At the transcriptomic level, we found differentially expressed genes between EOPE and CTRL, predominantly related to upregulation of immune activation pathways. Lastly, EOPE PBMCs induced heightened endothelial activation in vitro observed by increased ICAM-1 and ET-1 (p < 0.05), whereas LOPE PBMCs required LPS stimulation. Although significant proteomic changes are observed in the LOPE group, the EOPE displayed changes mostly at the transcriptomic levels and could induce endothelial activation in vitro.