The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL)

• Published in: International immunopharmacology Vol. 121; p. 110326
• Main Authors: Aslanian-kalkhoran, Lida, Kamrani, Amin, Alipourfard, Iraj, Chakari-Khiavi, Forough, Chakari-Khiavi, Aref, Aghebati-Maleki, Leili, Shekarchi, Ali Akbar, Mehdizadeh, Amir, Mojahedi, Maryam, Danaii, Shahla, Roshangar, Leila, Ahmadian Heris, Javad, Zolfaghari, Mohammadali, Dolati, Sanam, Soltani-Zangbar, Mohammad Sadegh, Yousefi, Mehdi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2023
• Subjects: Immunological disorders; LIT; Lymphocyte immunotherapy; Recurrent miscarriage; Recurrent pregnancy loss; NK cells; PMA; Tregs; PBMCs; RPL; uRPL; Recurrent miscarriage; HDL; APA; Th; ANA; Recurrent pregnancy loss; LDL; LIT; TGFβ; cDNA; Immunological disorders; FoxP3; Lymphocyte immunotherapy; RORγt; ELISA; BMI
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110326

•Recurrent pregnancy loss, also known as RPL, happens to 2–5% of women of reproductive age.•Immune system between the mother and the fetus plays an important role in the acceptance of the fetus and maintaining the pregnancy.•Modulation of the immune system by lymphocyte immunotherapy (LIT) is a reasonable way to prevent embryo rejection.•Pro-Inflammatory cytokines decline following subcutaneous LIT of women with RPL. In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.