ORIGINAL RESEARCH article

Front. Immunol.

Sec. Immunological Tolerance and Regulation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1568536

This article is part of the Research TopicInnate and Adaptive Immunity of Normal and Adverse PregnancyView all 4 articles

LYN and CYBB are related to inflammation-immunity in RSA

Provisionally accepted
Zhuna  WuZhuna WuQiuya  LinQiuya LinZhimei  ZhouZhimei ZhouYajing  XieYajing XieLi  HuangLi HuangLiying  ShengLiying ShengQiyang  ShiQiyang ShiYumin  KeYumin Ke*
  • Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

The final, formatted version of the article will be published soon.

Recurrent spontaneous abortion (RSA) seriously affects women's reproductive health, and its pathogenesis is complex and varied. The aim of this study is to identify key molecular markers closely associated with RSA to rapidly and effectively predict the RSA, and to provide simple and practical indicators for clinical diagnosis and treatment.We obtained mRNA expression profiles from the GEO database, immune-related genes (IRGs) from the ImmPort database, and genes related to inflammatory response from the LYN and CYBB are related to inflammation-immunity in RSA 2 Molecular Signatures database. Different Inflammation-and immunity-related genes (DIIRGs) were subjected to GO and KKEGG analysis.Protein-protein interaction (PPI) networks were utilized to explore the connections between various DIIRGs. The candidate DIIRGs were analyzed by the LASSO and the mSVM-RFE. The diagnostic ability of the candidate genes was verified using ROC curves. The performance of the predictive model was evaluated using a Nomo plot. We further confirmed the expression levels and diagnostic value of key genes by performing IHC in clinical tissue samples. The compositional patterns of the infiltration of 22 immune cell types in RSA were analyzed via the CIBERSORT algorithm.Result: We identified 403 differentially expressed genes (DEGs) and 7 DIIRGs between RSA endometrium and Non-RSA endometrium. GO analysis showed that DIIRGs were significantly enriched in positive regulation of cell-cell adhesion, inflammatory response to antigenic stimulus. KEGG enrichment analyses were performed mainly on Epithelial cell signaling in NOD-like receptor signaling pathway, and Ras signaling pathway. A predictive and diagnostic model composed of three genes. The CYBB, LYN, and MET genes were identified as diagnostic biomarkers of RSA, and reduced levels of CYBB and LYN expression were found to correlate with RSA in clinical samples. In addition, immune microenvironment analysis showed that CYBB and MET were positively correlated with naïve B cells and negatively correlated with CD8 T cells, LYN and MET were positively correlated with M2 macrophages and negatively correlated with eosinophils, respectively. CYBB and LYN are regarded as the crucial genes that constitute a model and contribute to inflammation-immunity in RSA. These findings provide a new perspective on the diagnosis and pathogenesis of RSA.

Keywords: Recurrent spontaneous abortion, cybB, lyn, Inflammation, Immunity

Received: 06 Feb 2025; Accepted: 03 Jun 2025.

Copyright: © 2025 Wu, Lin, Zhou, Xie, Huang, Sheng, Shi and Ke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yumin Ke, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

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