Title | Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Hong S, Banchereau R, Maslow B-SL, Guerra MM, Cardenas J, Baisch J, D Branch W, T Porter F, Sawitzke A, Laskin CA, Buyon JP, Merrill J, Sammaritano LR, Petri M, Gatewood E, Cepika A-M, Ohouo M, Obermoser G, Anguiano E, Kim TWhan, Nulsen J, Nehar-Belaid D, Blankenship D, Turner J, Banchereau J, Salmon JE, Pascual V |
Journal | J Exp Med |
Volume | 216 |
Issue | 5 |
Pagination | 1154-1169 |
Date Published | 2019 05 06 |
ISSN | 1540-9538 |
Keywords | Adult, Biomarkers, Embryo Implantation, Female, Humans, Longitudinal Studies, Lupus Erythematosus, Systemic, Pre-Eclampsia, Pregnancy, Pregnancy Complications, Prospective Studies, RNA-Seq, Transcriptome |
Abstract | Systemic lupus erythematosus carries an increased risk of pregnancy complications, including preeclampsia and fetal adverse outcomes. To identify the underlying molecular mechanisms, we longitudinally profiled the blood transcriptome of 92 lupus patients and 43 healthy women during pregnancy and postpartum and performed multicolor flow cytometry in a subset of them. We also profiled 25 healthy women undergoing assisted reproductive technology to monitor transcriptional changes around embryo implantation. Sustained down-regulation of multiple immune signatures, including interferon and plasma cells, was observed during healthy pregnancy. These changes appeared early after embryo implantation and were mirrored in uncomplicated lupus pregnancies. Patients with preeclampsia displayed early up-regulation of neutrophil signatures that correlated with expansion of immature neutrophils. Lupus pregnancies with fetal complications carried the highest interferon and plasma cell signatures as well as activated CD4 T cell counts. Thus, blood immunomonitoring reveals that both healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related signatures, and a lack thereof associates with adverse outcomes. |
DOI | 10.1084/jem.20190185 |
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Alternate Journal | J. Exp. Med. |
PubMed ID | 30962246 |
PubMed Central ID | PMC6504211 |
Grant List | R01 AR049772 / AR / NIAMS NIH HHS / United States P50 AR070594 / AR / NIAMS NIH HHS / United States R01 AR043727 / AR / NIAMS NIH HHS / United States R01 AR069572 / AR / NIAMS NIH HHS / United States U19 AI082715 / AI / NIAID NIH HHS / United States |