Evidence for maternal autoantibodies in the pathogenesis of preterm birth.

Rackaityte E; Borges B; Kortbawi HM; Miller HS; Shao SJ; Zorn KC; Caspar C; Wong R; McCarthy F; Creery JS; Mayer M; Raghavan M; Kouame E; Puccinelli RR; Kistler AL; Yu DJL; Ganem SR; DeRisi A; Kawaja Q; Wang CY; Saxena A; Oltman S; Kung AF; Mann SA; Mitchell A; Huang D; Rizzuto G; Rebecca J. Baer; Mandel-Brehm C; Ryckman KK; Gaw SL; Hillman SL; Jelliffe-Pawlowski LL; Halkias J; Sobhani NC; Anderson MS; Trespidi F; Alpini C; Bosoni T; Albertini R; Bellingeri C; Gardella B; Borghesi A; Prince N; Lasky-Su J; Michael R. Wilson; Cedars MI; Elias JE; MacKenzie TC; DeRisi JL

doi:10.1038/s41590-026-02689-y

Evidence for maternal autoantibodies in the pathogenesis of preterm birth.

Rackaityte E, Borges B, Kortbawi HM, Miller HS, Shao SJ, Zorn KC, Caspar C, Wong R, McCarthy F, Creery JS, Mayer M, Raghavan M, Kouame E, Puccinelli RR, Kistler AL, Yu DJL, Ganem SR, DeRisi A, Kawaja Q, Wang CY, Saxena A, Oltman S, Kung AF, Mann SA, Mitchell A, Huang D, Rizzuto G, Rebecca J. Baer, Mandel-Brehm C, Ryckman KK, Gaw SL, Hillman SL, Jelliffe-Pawlowski LL, Halkias J, Sobhani NC, Anderson MS, Trespidi F, Alpini C, Bosoni T, Albertini R, Bellingeri C, Gardella B, Borghesi A, Prince N, Lasky-Su J, Michael R. Wilson, Cedars MI, Elias JE, MacKenzie TC, DeRisi JL

Nature immunology · 2026 · doi:10.1038/s41590-026-02689-y · PMID:42875547 · PMC13710164

OA: gold CC-BY-4.0

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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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organisms 42

human mus sp. human human human rhesus monkeys streptococcus sp. group b rodents mus sp. rodents transgenic mice human naine d'afrique de l'ouest naine d'afrique de l'ouest human mus sp. transgenic mice human human human t7 bacteriophage human naine d'afrique de l'ouest rabbits human zitter rats human rabbits zitter rats naine d'afrique de l'ouest human human transgenic mice transgenic mice multicellular animals transgenic mice transgenic mice humans mus sp. human noordeloos 2009062 transgenic mice

chemicals 21

isoflurane formaldehyde haematoxylin nitrogen urea disulfide thioredoxin dithiol urea peptide formic acid formic acid peptide peptide peptide formic acid acetonitrile pentanol nitrogen acetone peptide nitrocellulose

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