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Communication

Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder

by
Luca Marozio
1,*,
Anna Maria Nuzzo
2,
Eugenio Gullo
1,
Laura Moretti
2,
Emilie M. Canuto
1,
Annalisa Tancredi
1,
Margherita Goia
3,
Stefano Cosma
1,
Alberto Revelli
4,
Alessandro Rolfo
2 and
Chiara Benedetto
1
1
Department of Surgical Sciences, Obstetrics and Gynecology 1, University of Turin, Via Ventimiglia 1, 10126 Turin, Italy
2
Department of Surgical Sciences, University of Turin, Via Ventimiglia 1, 10126 Turin, Italy
3
Unit of Pathology, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
4
Department of Surgical Sciences, Obstetrics and Gynecology 2, University of Turin, Via Ventimiglia 1, 10126 Turin, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(17), 13071; https://doi.org/10.3390/ijms241713071
Submission received: 16 July 2023 / Revised: 17 August 2023 / Accepted: 21 August 2023 / Published: 22 August 2023
(This article belongs to the Special Issue A Molecular Perspective on Reproductive Health)
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Abstract

Recurrent pregnancy loss (RPL) refers to two or more miscarriages before 20 weeks gestation. Its prevalence is 1–2%; its pathogenesis remains unexplained in more than 50% of cases, in which the cause is thought to be abnormal immune activity during placentation leading to a lack of pregnancy-induced immune tolerance. It is unknown whether immune activity is deranged in the endometrium of women with RPL. We studied the gene expression and the quantitative tissue protein levels of three immune checkpoints (CD276, which enhances cytotoxic T-cell activity, cytotoxic T-lymphocyte-associated antigen-4 [CTL-4], which reduces Th1 cytokine production, and lymphocyte activation gene-3 [LAG-3], which shows suppressive activity on Tregs and CD4+ T-cells) in endometrial samples from 27 women with unexplained RPL and in 29 women with dysfunctional uterine bleeding and previous uneventful pregnancies as controls. RNA isolation, real-time PCR, protein isolation, and ELISA were performed. CD276 gene expression and protein tissue levels were significantly lower in the endometrium of the RPL group than in the controls, whereas both CTL-4 and LAG-3 were significantly higher. This difference suggests defective endometrial immune regulation and overactivation of immune response in women with a history of RPL, at least in relation to controls with dysfunctional uterine bleeding and previous normal reproductive history.
Keywords: recurrent pregnancy loss; endometrium; immune activity; placentation; T-cell activity; pregnancy; immune tolerance recurrent pregnancy loss; endometrium; immune activity; placentation; T-cell activity; pregnancy; immune tolerance

Share and Cite

MDPI and ACS Style

Marozio, L.; Nuzzo, A.M.; Gullo, E.; Moretti, L.; Canuto, E.M.; Tancredi, A.; Goia, M.; Cosma, S.; Revelli, A.; Rolfo, A.; et al. Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder. Int. J. Mol. Sci. 2023, 24, 13071. https://doi.org/10.3390/ijms241713071

AMA Style

Marozio L, Nuzzo AM, Gullo E, Moretti L, Canuto EM, Tancredi A, Goia M, Cosma S, Revelli A, Rolfo A, et al. Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder. International Journal of Molecular Sciences. 2023; 24(17):13071. https://doi.org/10.3390/ijms241713071

Chicago/Turabian Style

Marozio, Luca, Anna Maria Nuzzo, Eugenio Gullo, Laura Moretti, Emilie M. Canuto, Annalisa Tancredi, Margherita Goia, Stefano Cosma, Alberto Revelli, Alessandro Rolfo, and et al. 2023. "Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder" International Journal of Molecular Sciences 24, no. 17: 13071. https://doi.org/10.3390/ijms241713071

APA Style

Marozio, L., Nuzzo, A. M., Gullo, E., Moretti, L., Canuto, E. M., Tancredi, A., Goia, M., Cosma, S., Revelli, A., Rolfo, A., & Benedetto, C. (2023). Immune Checkpoints in Recurrent Pregnancy Loss: New Insights into a Detrimental and Elusive Disorder. International Journal of Molecular Sciences, 24(17), 13071. https://doi.org/10.3390/ijms241713071

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