The dysregulation of immunological mechanisms normally engaged in the maintenance of a term pregnancy is increasingly implicated in the pathogenesis of preterm birth and other pregnancy-related complications ( 2– 4). These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.ĭuring pregnancy, the maternal immune system must engage in a fine balancing act: maintaining tolerance to the fetal allograft while preserving innate and adaptive immune mechanisms for protection against microbial challenges ( 1, 2). Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2–dependent STAT5ab signaling pathway in modulating T cell function during pregnancy.
Cell signaling–based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy.
Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. The maintenance of pregnancy relies on finely tuned immune adaptations.
El-Sayed, Cecele Quaintance, Ronald Gibbs, Gary L. Gaudilliere, … Show All …, Quentin Baca, Leslie McNeil, Robin Okada, Mohammad S. Tsai, Martha Tingle, Sofie Van Gassen, Dyani K.