Evidence for maternal autoantibodies in the pathogenesis of preterm birth.

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

Published in

Nature immunology. Oct 14, 2026. Epub Oct 14, 2026.

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.

PMID:
42875547
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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