Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy

Seunghee Hong, Romain Banchereau, Bat Sheva L. Maslow, Marta M. Guerra, Jacob Cardenas, Jeanine Baisch, D. Ware Branch, T. Flint Porter, Allen Sawitzke, Carl A. Laskin, Jill P. Buyon, Joan Merrill, Lisa R. Sammaritano, Michelle Petri, Elizabeth Gatewood, Alma Martina Cepika, Marina Ohouo, Gerlinde Obermoser, Esperanza Anguiano, Tae Whan KimJohn Nulsen, Djamel Nehar-Belaid, Derek Blankenship, Jacob Turner, Jacques Banchereau, Jane E. Salmon, Virginia Pascual

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1154-1169
Number of pages16
JournalJournal of Experimental Medicine
Volume216
Issue number5
DOIs
Publication statusPublished - 2019 May 1

Bibliographical note

Funding Information:
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health awards R01 AR49772 and R01 AR49772-07S2 (J.E. Salmon), R01 AR69572 and AR43727 (M. Petri), National Institute of Allergy and Infectious Diseases/National Institutes of Health award U19 AI082715 (V. Pascual), P50AR070594 (V. Pascual and J. Banchereau), the Morris and Alma Schapiro Fund (J.E. Salmon), the Baylor-Scott & White Health Care Research Foundation, and the Kathryn W. Davis gift to the Jackson Laboratory.

Publisher Copyright:
© 2019 Hong et al.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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