{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:36:49Z","timestamp":1768567009524,"version":"3.49.0"},"posted":{"date-parts":[[2024,10,4]]},"group-title":"Obstetrics and Gynecology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Complications from preterm birth are the leading cause of global mortality in children under age five\n                  <jats:sup>1,2<\/jats:sup>\n                  . Spontaneous preterm labor is the most common cause of preterm delivery and is associated with a breakdown of maternal-fetal tolerance\n                  <jats:sup>3\u20135<\/jats:sup>\n                  . However, the current understanding of the role of autoantibodies in this process has been limited to a handful of examples of pathogenic antibodies that occur with pregnancy complications\n                  <jats:sup>6\u201314<\/jats:sup>\n                  . Here, we employ proteome-wide autoantibody profiling via phage display immunoprecipitation and sequencing (PhIP-seq) to identify autoreactivities associated with pregnancy as well as term or preterm delivery outcomes in maternal sera across eight cohorts of human pregnancy (n=2,194). We find that preterm pregnancies exhibit greater proteome-wide autoreactivity, validated by placental proteome immunoprecipitation mass spectrometry analysis using patient sera. Within the preterm birth associated autoreactive signature, we find enrichment for pathways known to be critical for normal pregnancy outcomes, including vascular development, reproductive hormones, and regulators of inflammation. Further analysis of autoreactive targets revealed involvement of the IL1\u03b2 inflammatory cytokine cascade. IL1\u03b2 is one of the few inflammatory cytokines sufficient to rapidly induce labor in animals\n                  <jats:sup>15\u201324<\/jats:sup>\n                  and it is also elevated in preterm human pregnancies\n                  <jats:sup>25\u201329<\/jats:sup>\n                  . Across these eight cohorts, antibodies to cytokine IL1 receptor antagonist (IL1RA), a natural antagonist to IL1\u03b2 are significantly enriched in roughly 7% of preterm pregnancies. Sera from these patients functionally neutralize IL1RA activity\n                  <jats:italic>in vitro<\/jats:italic>\n                  and anti-IL1RA induces greater resorption, inflammation, and vascular malperfusion in timed-pregnant mice\n                  <jats:italic>in vivo<\/jats:italic>\n                  . These findings suggest utility for serologic diagnostics as one approach to stratify risk of spontaneous preterm delivery in addition to interventional strategies for restoring control of IL1\u03b2 during pregnancy.\n                <\/jats:p>","DOI":"10.1101\/2024.10.03.24314850","type":"posted-content","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T19:15:12Z","timestamp":1728069312000},"source":"Crossref","is-referenced-by-count":0,"title":["Evidence for Maternal Autoantibodies in the Pathogenesis of Preterm Birth"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3889-8082","authenticated-orcid":false,"given":"Elze","family":"Rackaityte","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6730-0398","authenticated-orcid":false,"given":"Beltran","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Francisco, San Francisco, CA USA"},{"name":"Center for Maternal-Fetal Precision Medicine, University of California San Francisco, San Francisco, CA USA"},{"name":"The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6482-0724","authenticated-orcid":false,"given":"Hannah M.","family":"Kortbawi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0920-7169","authenticated-orcid":false,"given":"Haleigh S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley J.","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Reproductive Sciences, University of California, San Francisco, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey C.","family":"Zorn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette","family":"Caspar","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 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