Evidence for maternal autoantibodies in the pathogenesis of preterm birth
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Nature Immunology
Authors: Elze Rackaityte, Beltran Borges, Hannah M. Kortbawi, Haleigh S. Miller, Shirley J. Shao, Kelsey C. Zorn, Colette Caspar, Rebecca Wong, Frank McCarthy, Joseph S. Creery, Margareta Mayer, Madhura Raghavan, Elaine Kouame, Robert R. Puccinelli, Amy L. Kistler, David J. L. Yu, Sammer Roach Ganem, Alexandra DeRisi, Quinn Kawaja, Chung-Yu Wang, Aditi Saxena, Scott Oltman, Andrew F. Kung, Sabrina A. Mann, Anthea Mitchell, David Huang, Gabrielle Rizzuto, Rebecca J. Baer, Caleigh Mandel-Brehm, Kelli K. Ryckman, Stephanie L. Gaw, Sara L. Hillman, Laura L. Jelliffe-Pawlowski, Joanna Halkias, Nasim C. Sobhani, Mark S. Anderson, Francsesca Trespidi, Claudia Alpini, Tiziana Bosoni, Riccardo Albertini, Camilla Bellingeri, Barbara Gardella, Alessandro Borghesi, Nicole Prince, Jessica Lasky-Su, Michael R. Wilson, Marcelle I. Cedars, Joshua E. Elias, Tippi C. MacKenzie, Joseph L. DeRisi
Institutions: University of California, San Francisco, Broad Center, Chan Zuckerberg Biohub San Francisco, University of California, Berkeley, Global Brain Health Institute, Memorial Sloan Kettering Cancer Center, University of California San Diego, Indiana University Bloomington, Indiana University, University College London, University of Pavia, Policlinico San Matteo Fondazione, École Polytechnique Fédérale de Lausanne, University of Geneva, University Hospital of Geneva, Brigham and Women's Hospital, Harvard University, Chan Zuckerberg Initiative (United States)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7221807376