Reproductive System and Pregnancy Open access Peer reviewed

Comprehensive analysis of HLA-G expression, hormonal profiles, and inflammatory markers in women with recurrent pregnancy loss

Simi Nadarajan, Arumugam Suresh, D Roy, Natrajan Muninathan and 3 more

Hormone Molecular Biology and Clinical Investigation | Aug 18, 2026

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Investigating the role of Human Leukocyte Antigen-G gene expression, inflammatory cytokines, and hormonal profiles in the pathogenesis of recurrent pregnancy loss highlighted the interplay between immune dysfunction, hormonal imbalance, and reduced HLA-G expression in RPL.

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OBJECTIVES: This study aimed to investigate the role of Human Leukocyte Antigen-G (HLA-G) gene expression, inflammatory cytokines, and hormonal profiles in the pathogenesis of recurrent pregnancy loss (RPL) and to assess their potential as diagnostic and predictive markers. METHODS: A case-control study was conducted involving 240 women, including 120 with clinically confirmed RPL and 120 fertile controls. Serum levels of CRP (C-reactive protein) and IL-6 (interleukin-6) were measured using enzyme-linked immunosorbent assay (ELISA). Hormonal parameters, including thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed using chemiluminescence immunoassays (CLIA). HLA-G gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analyses included t-tests, receiver operating characteristic (ROC) curve analysis, and logistic regression to identify independent predictors. RESULTS: RPL cases showed significantly higher levels of TSH, FSH, CRP, and IL-6 and markedly lower HLA-G gene expression compared with controls (p < 0.001). CRP showed the highest diagnostic accuracy (AUC = 0.997), followed by HLA-G (AUC = 0.938) and IL-6 (AUC = 0.896). Logistic regression identified IL-6, FSH, TSH, and HLA-G as independent predictors of RPL. CONCLUSIONS: The findings highlight the interplay between immune dysfunction, hormonal imbalance, and reduced HLA-G expression in RPL. These markers may help in the early identification and risk assessment of RPL, with HLA-G showing potential for further investigation as a therapeutic target.

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Simi Nadarajan

first | Meenakshi Academy of Higher Education and Research

Arumugam Suresh

middle | Meenakshi Academy of Higher Education and Research | ORCID 0000-0001-6247-1156

D Roy

middle | Centre For Development Studies | ORCID 0009-0005-7124-148X

Natrajan Muninathan

middle | Meenakshi Academy of Higher Education and Research

Venugopal Gopikrishnan

middle | Sathyabama Institute of Science and Technology | ORCID 0000-0003-2336-7043

Jeena Jose

middle | Meenakshi Academy of Higher Education and Research | ORCID 0000-0002-5664-5495

Aswathi Palakkattu Veetil

last | Meenakshi Academy of Higher Education and Research | ORCID 0009-0007-9857-9426

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BibTeX

@article{Nadarajan2026Comprehensive,
  title = {Comprehensive analysis of HLA-G expression, hormonal profiles, and inflammatory markers in women with recurrent pregnancy loss},
  author = {Simi Nadarajan and Arumugam Suresh and D Roy and Natrajan Muninathan and Venugopal Gopikrishnan and Jeena Jose and Aswathi Palakkattu Veetil},
  journal = {Hormone Molecular Biology and Clinical Investigation},
  year = {2026},
  doi = {10.1515/hmbci-2026-0014},
  url = {https://doi.org/10.1515/hmbci-2026-0014}
}

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