Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy
| Autor: | Alma-Martina Cepika, Allen D. Sawitzke, Seunghee Hong, Marta M. Guerra, Jill P. Buyon, Joan T. Merrill, Bat Sheva L. Maslow, Marina Ohouo, Derek Blankenship, Djamel Nehar-Belaid, Virginia Pascual, Michelle Petri, Gerlinde Obermoser, Jane E. Salmon, Jacques Banchereau, Jeanine Baisch, John Nulsen, D. Ware Branch, Romain Banchereau, Lisa R. Sammaritano, Tae Whan Kim, Jacob Cardenas, Carl A. Laskin, Esperanza Anguiano, Elizabeth Gatewood, T. Flint Porter, Jacob Turner |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Immunology Plasma cell News Insights Article Preeclampsia Transcriptome 03 medical and health sciences 0302 clinical medicine Immune system Pre-Eclampsia immune system diseases Pregnancy medicine Immunology and Allergy Lupus Erythematosus Systemic Animals Humans Embryo Implantation Longitudinal Studies Prospective Studies RNA-Seq skin and connective tissue diseases Research Articles 030304 developmental biology Inflammation 0303 health sciences Fetus Lupus erythematosus Systemic lupus erythematosus Wolves business.industry medicine.disease 3. Good health Pregnancy Complications medicine.anatomical_structure Female business Biomarkers 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Healthy and uncomplicated lupus pregnancies exhibit early and sustained transcriptional modulation of lupus-related pathways. This might contribute to fetal tolerance while predisposing pregnant women to certain infections. Failure to modulate these pathways is associated with lupus pregnancy complications. 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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