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Multimodal immune phenotyping of maternal peripheral blood in normal human pregnancy
Richard Apps, … , John S. Tsang, Christa S. Zerbe
Richard Apps, … , John S. Tsang, Christa S. Zerbe
Published March 12, 2020
Citation Information: JCI Insight. 2020;5(7):e134838. https://doi.org/10.1172/jci.insight.134838.
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Research Article Immunology Reproductive biology

Multimodal immune phenotyping of maternal peripheral blood in normal human pregnancy

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Abstract

Changes in maternal immunity during pregnancy can result in an altered immune state, and as a natural perturbation, this provides an opportunity to understand functional interactions of the immune system in vivo. We report characterization of maternal peripheral immune phenotypes for 33 longitudinally sampled normal pregnancies, using clinical measurements of complete blood counts and major immune cell populations, as well as high parameter flow cytometry for 30 leukocyte antigens characterizing 79 cell populations, and monitoring of 1305 serum proteins using the SomaLogic platform. Cellular analyses characterized transient changes in T cell polarization and more persistent alterations in T and B cell subset frequencies and activation. Serum proteomic analysis identified a potentially novel set of 7 proteins that are predictive of gestational age: DDR1, PLAU, MRC1, ACP5, ROBO2, IGF2R, and GNS. We further show that gestational age can be predicted from the parameters obtained by complete blood count tests and clinical flow cytometry characterizing 5 major immune cell populations. Inferring gestational age from this routine clinical phenotyping data could be useful in resource-limited settings that lack obstetric ultrasound. Overall, both the cellular and proteomic analyses validate previously reported phenotypic immunological changes of pregnancy and uncover potentially new alterations and predictive markers.

Authors

Richard Apps, Yuri Kotliarov, Foo Cheung, Kyu Lee Han, Jinguo Chen, Angélique Biancotto, Ashley Babyak, Huizhi Zhou, Rongye Shi, Lisa Barnhart, Sharon M. Osgood, Yasmine Belkaid, Steven M. Holland, John S. Tsang, Christa S. Zerbe

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Figure 2

Changes in peripheral blood immune populations throughout pregnancy.

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Changes in peripheral blood immune populations throughout pregnancy.
(A)...
(A) Using all 33 subjects in our study, longitudinal comparisons between visits 1 and 3 (early and late gestation), visits 3 and 4 (late gestation and postpartum), or visits 1 and 4 (early gestation and postpartum) identified 32 subsets of immune cell populations with fold change greater than 1.2 or less than 0.8 and significant differences for at least 1 comparison using Wilcoxon’s signed-rank paired tests (*FDR < 0.05, **FDR < 0.01, and ***FDR < 0.001). T c/s, CD8+ T cells (cytotoxic/suppressors). (B) For representative populations that demonstrated different patterns of change, fold changes compared with visit 1 are shown for all 4 visits studied. Type 2 CD4+ Tfh cells increased during gestation and declined after parturition. (C) Type 1/17 Tfh cells decreased during gestation and rebounded after parturition. (D) Transitional B cells declined significantly during gestation but increased much more strongly after parturition. See A for FDR-adjusted P values.

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