Effects of peripheral blood mononuclear cell immunotherapy on immunological, oxidative stress, and molecular markers in recurrent pregnancy loss

Immune dysregulation contributes to pregnancy complications, including recurrent pregnancy loss (RPL). Lymphocyte immunotherapy (LIT) is used to modulate abnormal maternal immune responses. This study aimed to evaluate the immunologic parameters between infected and non-infected RPL patients and the effects of LIT on immunologic abnormalities. This study included 100 women with RPL, comprising patients with and without microbial infections. Following blood collection, PBMCs and serum were isolated to evaluate the expression of miRNAs, oxidative stress-related markers, pro-inflammatory cytokines, neutrophil, lymphocyte count, and NLR. RPL patients without microbial infections received immunotherapy, and the same parameters were evaluated and compared with non-treated groups. The neutrophil count ( p < 0.0001), NLR ( p = 0.033), relative expression of miR-96 ( p < 0.0001), oxidative stress-related markers (elastase ( p = 0.0003), MPO ( p = 0.0005), NO ( p < 0.0001), iNOS ( p = 0.0005)) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were significantly higher in PBMCs and sera of infected-RPL women, than in those without infection. Immunotherapy significantly decreased the expression of miR-96 ( p < 0.0001), oxidative stress-related enzymes (elastase ( p = 0.0076), MPO ( p = 0.0034), NO ( p = 0.0012), iNOS ( p = 0.0088)), and cytokines (TNF-α, IL-1β, and IL-6) in comparison with non-treated groups. PBMC therapy may modulate aberrant immune responses, including dysregulated immune-related miRNA expression, while reducing elevated levels of pro-inflammatory cytokines and oxidative stress-related markers. However, NLR and neutrophil count were not affected by this approach, suggesting that more practical studies are needed in this field.