Human Chorionic Gonadotrophin As a Potencial Immune Modulator in Patients with Multiple Sclerosis

CORREALE, JORGE; VALEFF, NATALÍN; JENSEN, FEDERICO; VENTIMIGLIA, MARÍA SILVIA; QUIROGA, MARÍA FLORENCIA; JURIOL LORENA VANESA

San Diego

Otro; ACTRIMS forum 2018; 2018

Americas Committee for Treatment and Research in Multiple Sclerosis

Background:Multiple sclerosis (MS) is 2-3 times more common in women than men. It is well known that pregnancy has a strong influence on MS disease activity and a reduced relapse frequency (70%) is seen during pregnancy. After delivery, MS symptoms often worsen, with frequent relapses in the postpartum period and highest relapse frequency within 3 months after delivery. Hormonal factors are thus assumed to be involved in regulating the course of the disease. Human chorionic gonadotropin (hCG) is synthetized by the placenta during pregnancy and the presence of its receptor has been described in immune cells, such as B and T cells.Objectives:To evaluate the potential capacity of hCG to regulate activation and cytokine production by immune cells in a context of MS.Methods:We recruited women suffering MS from 20-40 years old to obtain whole blood samples. PBMC were isolated and then cultivated with hCG (third trimester levels), either urinary (u, 100 IU/ml) or recombinant (r, 5 ug/ml) or without hCG (control) for 24 h. PMA, Ionomycin and Brefeldin A were added, in some wells, for the last 5h of culture. Flow cytometry was used for the phenotypical characterization of the lymphocytes subset: CD19, CD80, CD86 (B cells), CD4 and Foxp3 (T cells) and to evaluate intracellular cytokines levels: TNF-α and IL-10.Results:We observed that treatment with hCGu significantly reduced the relative numbers of CD19+CD86+ B cells as compared to control group. No changes were observed concerning CD80+ expressing B-lymphocytes. Interestingly, addition of either hCGu or hCGr induced a significant increase in the total number of CD4+Foxp3+IL-10+ regulatory T cells upon stimulation, when compared to controls. Similarly, IL-10 production by CD19+ B cells stimulated with either type of hCG, showed a slight no significant increase. On the other hand, treatment with either hCGu or hCGr, also induced a significant reduction in the total numbers of CD19+TNF-α+ B cells as well as CD4+TNF-α+ cells, as compared to controls (data were analyzed by One-way ANOVA).Conclusion:Overall, we demonstrated here that treatment with hCG in vitro, lowers the expression of the costimulatory molecule CD86 in B cells, increases the production of IL-10 by CD4+Foxp3+ regulatory T cells and decreases the production of TNF-α, in both CD4+ and CD19+ B cells. These results open new avenues to explore the use of hCG as a potential treatment in MS patients, especially for those that do not respond to conventional therapies.