Avaliação da molécula de checkpoint HLA-G e da resposta Th1, Th2 E Th17 em mulheres com infertilidade

Abstract

The search for biomarkers with predictive and prognostic value in the pathophysiology of infertility among couples is one of the objectives in the field of reproductive immunology. It is known that immunoregulatory molecules and the expression of pro and anti-inflammatory mediators contribute to reproductive medicine. However, the role of these molecules in infertility is not yet fully understood. In this context, this study aims to evaluate the expression of the HLA-G checkpoint molecule and the levels of cytokines of the Th1, Th2, and Th17 profiles in serum and Follicular Fluid (FF) in infertile women undergoing In Vitro Fertilization (IVF). This study included 75 women who signed the Informed Consent Form (ICF) and were subsequently stratified into two groups. The IVF group (n=39) consisted of women undergoing IVF recruited at the Center for Assisted Reproduction (CAR) of a teaching hospital. The control group (n=36) consisted of women who had at least one pregnancy with a live birth. The HLA-G molecule was quantified in the peripheral blood of all study participants using PE-conjugated anti-HLA-G antibody, and cytokine quantification was performed in the serum and FF of participants using the Cytokine Bead Assay kit. Flow cytometry was used as the quantification technique in both tests. As a result, there was lower expression of HLA-G in lymphocytes (p=0.0001) and granulocytes (p= 0.0191) in the IVF group compared to the control group. In addition, HLA-G+ lymphocytes correlated with fertilization rate (p=0.0359). Regarding cytokines, there was a higher amount of IL-2 (p=0.0012), IL-17 (p=0.0021), IL-6 (p=0.0009), IL-10 (p=0.0004), and IL-4 (p=0.0019) in the serum of IVF group patients compared to the control group, as well as a higher amount of IL-17 (p=0.0001), IL-6 (p=<0.0001), IL-10 (p=<0.0001) in the FF compared to serum in the group of infertile women. These results indicate an important role of these molecules in immunomodulation in the context of infertility. This is the first study to associate the Th1, Th2, and Th17 response profiles and the HLAG molecule in different infertility conditions in the IVF scenario.