Peripheral blood subpopulations of Bregs producing IL-35 in women with endometriosis.

PROBLEM: Interleukin 35 (IL-35) is involved in the pathogenesis of endometriosis by suppressing immunoreaction and promoting endometrial cell proliferation. It may also be an essential cytokine in forming the immunosuppressive functions of regulatory B lymphocytes (Bregs). The involvement of Bregs in the pathogenesis of endometriosis has not been previously investigated. In this study, we determined the frequencies of different Breg subpopulations, namely, B10, immature B-cells, and plasmablasts, and their abilities to produce IL-35 in women with endometriosis compared to healthy women. METHODS: The frequencies of different subpopulations of Bregs producing IL-35 were measured in the peripheral blood of women with endometriosis (total pool), women with deep infiltration endometriosis (DIE), women with ovarian endometriosis, and healthy women as a control by flow cytometry. RESULTS: We observed a decrease in the percentage of B10 cells and plasmablasts in women with endometriosis and an increase in the percentage of these Breg populations producing IL-35 in the same experimental group. Interestingly, we also revealed that women with DIE had increased percentages of B10 cells and plasmablasts producing IL-35. CONCLUSION: Taken together, our findings are the first to reveal the frequencies of different subpopulations of Bregs producing IL-35 in women with endometriosis. The results suggest that IL-35 expression in B lymphocytes could be used as a peripheral marker of endometriosis; however, further studies are needed.

Fibronectin Molecular Status in Plasma of Women with Endometriosis and Fertility Disorders.

The diagnosis of endometriosis and fertility disorders is difficult; therefore, it is necessary to look for reliable biomarkers. Analysis of the molecular status of fibronectin as a key player in repair and wound healing processes, as well as in coagulation and fibrinolysis pathways, is justified. ELISA and SDS-agarose immunoblotting were applied to determine the fibronectin concentration and presence and occurrence of soluble FN-fibrin complexes in the blood plasma of women with endometriosis (n = 38), fertility disorders (n = 28) and the healthy group (n = 25). The concentration of fibronectin in the blood plasma of women with endometriosis (292.61 ± 96.17 mg/L) and fertility disorders (287.53 ± 122.68 mg/L) was significantly higher than in the normal group (226.55 ± 91.98 mg/L). The presence of FN-fibrin complexes of 750, 1000, 1300, 1600 and 1900 kDa in the plasma of women with endometriosis and fertility disorders was shown. The presence of FN-fibrin complexes with a molecular mass of more than 1300 kDa in women with endometriosis and infertility and the complete absence of these complexes in healthy women may indicate an increased and chronic activation of coagulation mechanisms in these patients. The presence of complexes of high molecular mass may be one of the biomarkers of fertility disorders in women.