Peer-reviewedCC BY 4.0Nature Immunology
Evidence for maternal autoantibodies in the pathogenesis of preterm birth
26 affiliations
- 1Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA USA
- 2Department of Surgery, University of California San Francisco, San Francisco, CA USA
- 3Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, CA USA
- 4The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA USA
- 5Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA USA
- 6Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA USA
- 7Chan Zuckerberg Biohub San Francisco, San Francisco, CA USA
- 8Division of Neonatology, Department of Pediatrics, University of California San Francisco, San Francisco, CA USA
- 9UC Berkeley - UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA USA
- 10Diabetes Center, School of Medicine, University of California San Francisco, San Francisco, CA USA
- 11Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA USA
- 12UCSF California Preterm Birth Initiative, San Francisco, CA USA
- 13UCSF Institute for Global Health Studies, San Francisco, CA USA
- 14Immuno-Oncology Program and Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA
- 15Department of Pediatrics, University of California San Diego, La Jolla, CA USA
- 16Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN USA
- 17Maternal and Fetal Medicine Department, Institute for Women’s Health, University College London, London, UK
- 18Host-Pathogen Interaction Group and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- 19Medical Genetics, Department of Molecular Medicine, University of Pavia, Pavia, Italy
- 20School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland
- 21Laboratory of Biochemical-Clinical Analyses, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- 22Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- 23Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- 24Neonatal and Pediatric Intensive Care Unit, Mother, Child and Adolescent Department, Geneva University Hospitals, Geneva, Switzerland
- 25Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland
- 26Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA USA
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.
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BibTeX
@article{rackaityte2026evidence,
title = {{Evidence for maternal autoantibodies in the pathogenesis of preterm birth}},
author = {Elze Rackaityte and Beltran Borges and Hannah M. Kortbawi and Haleigh S. Miller and Shirley J. Shao and Kelsey C. Zorn and Colette Caspar and Rebecca Wong and Frank McCarthy and Joseph S. Creery and Margareta Mayer and Madhura Raghavan and Elaine Kouame and Robert R. Puccinelli and Amy L. Kistler and David J. L. Yu and Sammer Roach Ganem and Alexandra DeRisi and Quinn Kawaja and Chung-Yu Wang and Aditi Saxena and Scott Oltman and Andrew F. Kung and Sabrina A. Mann and Anthea Mitchell and David Huang and Gabrielle Rizzuto and Rebecca J. Baer and Caleigh Mandel-Brehm and Kelli K. Ryckman and Stephanie L. Gaw and Sara L. Hillman and Laura L. Jelliffe-Pawlowski and Joanna Halkias and Nasim C. Sobhani and Mark S. Anderson and Francsesca Trespidi and Claudia Alpini and Tiziana Bosoni and Riccardo Albertini and Camilla Bellingeri and Barbara Gardella and Alessandro Borghesi and Nicole Prince and Jessica Lasky-Su and Michael R. Wilson and Marcelle I. Cedars and Joshua E. Elias and Tippi C. MacKenzie and Joseph L. DeRisi},
journal = {Nature Immunology},
year = {2026},
month = oct,
doi = {10.1038/s41590-026-02689-y},
url = {https://doi.org/10.1038/s41590-026-02689-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evidence for maternal autoantibodies in the pathogenesis of preterm birth
AU - Elze Rackaityte
AU - Beltran Borges
AU - Hannah M. Kortbawi
AU - Haleigh S. Miller
AU - Shirley J. Shao
AU - Kelsey C. Zorn
AU - Colette Caspar
AU - Rebecca Wong
AU - Frank McCarthy
AU - Joseph S. Creery
AU - Margareta Mayer
AU - Madhura Raghavan
AU - Elaine Kouame
AU - Robert R. Puccinelli
AU - Amy L. Kistler
AU - David J. L. Yu
AU - Sammer Roach Ganem
AU - Alexandra DeRisi
AU - Quinn Kawaja
AU - Chung-Yu Wang
AU - Aditi Saxena
AU - Scott Oltman
AU - Andrew F. Kung
AU - Sabrina A. Mann
AU - Anthea Mitchell
AU - David Huang
AU - Gabrielle Rizzuto
AU - Rebecca J. Baer
AU - Caleigh Mandel-Brehm
AU - Kelli K. Ryckman
AU - Stephanie L. Gaw
AU - Sara L. Hillman
AU - Laura L. Jelliffe-Pawlowski
AU - Joanna Halkias
AU - Nasim C. Sobhani
AU - Mark S. Anderson
AU - Francsesca Trespidi
AU - Claudia Alpini
AU - Tiziana Bosoni
AU - Riccardo Albertini
AU - Camilla Bellingeri
AU - Barbara Gardella
AU - Alessandro Borghesi
AU - Nicole Prince
AU - Jessica Lasky-Su
AU - Michael R. Wilson
AU - Marcelle I. Cedars
AU - Joshua E. Elias
AU - Tippi C. MacKenzie
AU - Joseph L. DeRisi
PY - 2026
DA - 2026/10/14
JO - Nature Immunology
DO - 10.1038/s41590-026-02689-y
UR - https://doi.org/10.1038/s41590-026-02689-y
AB - 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.
SN - 1529-2908
SN - 1529-2916
ER -