Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy

Author:

Hong Seunghee123,Banchereau Romain34,Maslow Bat-Sheva L.5ORCID,Guerra Marta M.6ORCID,Cardenas Jacob3,Baisch Jeanine123,Branch D. Ware78,Porter T. Flint78,Sawitzke Allen7,Laskin Carl A.9ORCID,Buyon Jill P.10,Merrill Joan11,Sammaritano Lisa R.612,Petri Michelle13ORCID,Gatewood Elizabeth3,Cepika Alma-Martina3,Ohouo Marina123ORCID,Obermoser Gerlinde3,Anguiano Esperanza3ORCID,Kim Tae Whan123,Nulsen John14,Nehar-Belaid Djamel5ORCID,Blankenship Derek3,Turner Jacob3ORCID,Banchereau Jacques5ORCID,Salmon Jane E.612,Pascual Virginia123ORCID

Affiliation:

1. Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY

2. Department of Pediatrics, Weill Cornell Medicine, New York, NY

3. Baylor Institute for Immunology Research, Dallas, TX

4. Oncology Biomarker Development, Genentech, South San Francisco, CA

5. The Jackson Laboratory for Genomic Medicine, Farmington, CT

6. Department of Medicine and Program in Inflammation and Autoimmunity, Hospital for Special Surgery, New York, NY

7. University of Utah Health Sciences Center, Salt Lake City, UT

8. Intermountain Healthcare, Salt Lake City, UT

9. Mount Sinai Hospital and the University of Toronto, Toronto, Ontario, Canada

10. New York University School of Medicine, New York, NY

11. Oklahoma Medical Research Foundation, Oklahoma City, OK

12. Department of Medicine, Weill Cornell Medicine, New York, NY

13. Johns Hopkins University School of Medicine, Baltimore, MD

14. University of Connecticut School of Medicine, Farmington, CT

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.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institutes of Health

National Institute of Allergy and Infectious Diseases

Baylor-Scott & White Health Care Research Foundation

Kathryn W. Davis

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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