Evidence for maternal autoantibodies in the pathogenesis of preterm birth

Preterm birth is associated with breakdown of maternal-fetal tolerance and remains the leading cause of global mortality in young children. However, the role of self-reactive antibodies has been limited to a handful of pathogenic allo- and autoantibodies linked to pregnancy complications. Here we identify a shared autoreactive signature of pregnancy in pregnant sera (n = 2,719) relative to never-pregnant controls (n = 130), using proteome-wide autoantibody profiling. Across eight human pregnancy cohorts, we define autoreactivities associated with preterm birth by comparing preterm (n = 688) and term (n = 1,505) pregnancies. Within the signature, antibodies to IL1 receptor antagonist (IL1RA) induce resorption, inflammation and vascular malperfusion in pregnant mice. IL1RA localizes to placental endothelial adherens junctions, suggesting a role in vascular integrity. These findings identify a term pregnancy humoral immune program and shared changes preceding preterm delivery, including anti-IL1RA, which may have direct pathogenic consequences.

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Publication Details

Journal
Nature Immunology
Published
2026-10-14
DOI
https://doi.org/10.1038/s41590-026-02689-y
Primary Topic
Reproductive System and Pregnancy
Type
article
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article

Evidence for maternal autoantibodies in the pathogenesis of preterm birth

Tiziana Bosoni, Shirley J. Shao, Sabrina A Mann, Kelsey C. Zorn et al.
Nature Immunology
Reproductive System and Pregnancy
article

Evidence for maternal autoantibodies in the pathogenesis of preterm birth

Tiziana Bosoni, Shirley J. Shao, Sabrina A Mann, Kelsey C. Zorn, Margareta Mayer, Joshua Eric Elias, Nasim C. Sobhani, Claudia Alpini, Jessica Ann Lasky-Su, Camilla Bellingeri, Rebecca J. Baer, Hannah M. Kortbawi, Michael R. Wilson, Frank M. McCarthy, Robert R. Puccinelli, Andrew F. Kung, Caleigh Mandel‐Brehm, Amy L. Kistler, Anthea M. Mitchell, Joseph L. DeRisi, Nicole Prince, Joseph S. Creery, Haleigh S. Miller, Scott P. Oltman, Elze Rackaityte, Elaine Kouame, Kelli K. Ryckman, David J. L. Yu, Beltran Borges, Tippi C. MacKenzie, Chung‐Yu Wang, Marcelle Ivonne Cedars, Alessandro Borghesi, Joanna Halkias, Sara L. Hillman, Gabrielle A. Rizzuto, Mark Stuart Anderson, Francesca Trespidi, Riccardo Albertini, Stephanie L. Gaw, Laura L. Jelliffe‐Pawlowski, Colette M. Caspar, Rebecca Wong, Quinn Kawaja, Barbara Gardella, Madhura Raghavan, Sammer Roach Ganem, David Huang, Alexandra DeRisi, Aditi Saxena
article en

Abstract

Preterm birth is associated with breakdown of maternal-fetal tolerance and remains the leading cause of global mortality in young children. However, the role of self-reactive antibodies has been limited to a handful of pathogenic allo- and autoantibodies linked to pregnancy complications. Here we identify a shared autoreactive signature of pregnancy in pregnant sera (n = 2,719) relative to never-pregnant controls (n = 130), using proteome-wide autoantibody profiling. Across eight human pregnancy cohorts, we define autoreactivities associated with preterm birth by comparing preterm (n = 688) and term (n = 1,505) pregnancies. Within the signature, antibodies to IL1 receptor antagonist (IL1RA) induce resorption, inflammation and vascular malperfusion in pregnant mice. IL1RA localizes to placental endothelial adherens junctions, suggesting a role in vascular integrity. These findings identify a term pregnancy humoral immune program and shared changes preceding preterm delivery, including anti-IL1RA, which may have direct pathogenic consequences.

Nature Immunology
University of Geneva (CH), Brigham and Women's Hospital (US), Memorial Sloan Kettering Cancer Center (US), Harvard University (US), University of California, San Francisco (US), University of Pavia (IT), University of California San Diego (US), Chan Zuckerberg Biohub San Francisco (US), University Hospital of Geneva (CH), Indiana University Bloomington (US), Chan Zuckerberg Initiative (United States) (US), Broad Center (US), Policlinico San Matteo Fondazione (IT), Global Brain Health Institute (US), University College London (GB), École Polytechnique Fédérale de Lausanne (CH), Indiana University (US), University of California, Berkeley (US)
Good health and well-being
Openalex Percentile: Top 20%
Reproductive System and Pregnancy
DOIOpen Access PDFOpenAlex
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