Compositions and methods of prognosis and classification for preeclampsia
Inventors
Gauilliere, Brice L. • Angst, Martin S. • Aghaeepour, Nima • Stevenson, David K. • Han, Xiaoyuan • Ghaemi, Mohammad S.
Assignees
Leland Stanford Junior University
Publication Number
US-12352765-B2
Publication Date
2025-07-08
Expiration Date
2039-11-14
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Abstract
Multiparametric analysis is performed at the single cell level of biological samples obtained from an individual during pregnancy to obtain a determination of changes in immune cell subsets, which changes include, without limitation, altered activation states of proteins involved in signaling pathways. Changes occur in signaling pathways of these immune cells that are predictive of propensity to develop preeclampsia in the pregnancy.
Core Innovation
The invention provides compositions and methods for classification, diagnosis, prognosis, theranosis, and prediction of outcomes during pregnancy with respect to development of preeclampsia. It involves multiparametric analysis at the single cell level of immune cell features obtained from biological samples collected from a pregnant individual at multiple timepoints during pregnancy. This analysis includes measuring altered activation states of proteins involved in immune signaling pathways, particularly profiling immune cell distributions and functional responses dynamically over time.
The problem being solved is that preeclampsia, a severe complication of pregnancy characterized by hypertension and organ dysfunction, lacks reliable early diagnostic tests. Currently, preeclampsia is only diagnosed after clinical signs and symptoms appear, which can be too late to prevent harm to the mother and fetus. The invention addresses the challenge of early detection by identifying dynamic changes in immune signaling pathways, such as decreased basal pSTAT5 levels in CD4+ T cells between first and second trimesters, which are predictive of a propensity to develop preeclampsia before clinical onset. This enables timely intervention and tailored treatments.
Claims Coverage
The patent presents two independent methods focused on analyzing immune cell signaling dynamics to predict and treat preeclampsia. The main inventive features include longitudinal measurement of basal pSTAT5 in CD4+ T cells or subsets thereof, assessing decreases between first and second trimesters, and treating identified individuals with aspirin or IL-2.
Longitudinal analysis of basal pSTAT5 in CD4+ T cells for preeclampsia prognosis and treatment
A method comprising obtaining immune cell-containing biological samples at two timepoints during pregnancy (first and second trimesters), measuring single cell basal levels of pSTAT5 in CD4+ T cells at these timepoints, detecting a decrease in basal pSTAT5 levels between first and second trimester samples indicative of propensity to develop preeclampsia, providing prognosis assessment, and treating the individual with aspirin or IL-2.
Longitudinal analysis of basal pSTAT5 in CD4+ T cell subsets for preeclampsia prognosis and treatment
A method comprising obtaining immune cell-containing biological samples at two timepoints during pregnancy (first and second trimesters), measuring single cell basal levels of pSTAT5 in specific subsets of CD4+ T cells (including CD4+Tbet+T cells, CD4+CD45RA+ T cells, or CD4+CD25+FoxP3+ Tregs) at these timepoints, detecting a decrease in basal pSTAT5 levels between first and second trimester samples indicative of propensity to develop preeclampsia, providing prognosis assessment, and treating the individual with aspirin or IL-2.
The claims cover methods of early prognosis of preeclampsia based on decreased basal pSTAT5 signaling in CD4+ T cells or subsets of these cells between first and second trimesters, coupled with treatment of identified individuals using aspirin or IL-2, with specific timing and sample types defined.
Stated Advantages
The methods enable early identification of women at high risk of developing preeclampsia well before clinical diagnosis, allowing for timely intervention.
Measurement of immune signaling dynamics provides more accurate prediction than static assessments or cell frequency alone.
The multiparameter immune cell profiling captures systemic immune dysfunction spanning innate and adaptive compartments, improving prognostic accuracy.
Early detection facilitates personalized treatment regimens, including low dose aspirin or IL-2, potentially preventing severe outcomes for mother and fetus.
Documented Applications
Prediction, prognosis, and classification of propensity to develop preeclampsia during pregnancy based on immune signaling dynamics.
Monitoring of immune cell signaling changes longitudinally during pregnancy for clinical decision making.
Therapeutic intervention planning including administration of low dose aspirin and low dose IL-2 to individuals identified at risk for preeclampsia.
Use of multiparameter mass cytometry or flow cytometry immunoassays applied to peripheral blood mononuclear cells or whole blood samples collected longitudinally from pregnant women.
Development and use of kits comprising affinity reagents for immune cell markers and signaling proteins to conduct the assays, optionally including software for data analysis and prognostic reporting.
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