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Longitudinal profiling of human blood transcriptome in healthy and lupuspregnancy

Author

Hong S#1,2,3, Banchereau R#3,4, Maslow BL#5, Guerra MM6, Cardenas J3, Baisch J1,2,3, Branch DW7,8, Porter TF7,8, Sawitzke A7, Laskin CA9, Buyon JP10, Merrill J11, Sammaritano LR6,12, Petri M13, Gatewood E3, Cepika AM3, Ohouo M1,2,3, Obermoser G3, Anguiano E3, Kim TW1,2,3, Nulsen J14, Nehar-Belaid D5, Blankenship D3, Turner J3, Banchereau J#5, Salmon JE#6,12, Pascual V#1,2,3. J Exp Med. 2019 May 6;216(5):1154-1169. doi: 10.1084/jem.20190185. Epub 2019 Apr 8.

Author Information

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.#Contributed equally

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.