Human chorionic gonadotrophin: the potential link between pregnancy improvement in the context of Multiple Sclerosis

JURIOL LORENA VANESA; SCHEPANSKI, STEVEN; CORREALE, JORGE; THIELE, KRISTIN; ARCK, PETRA; VALEFF, NATALÍN; VENTIMIGLIA, MARÍA SILVIA; JENSEN, FEDERICO

Estocolmo

Congreso; 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis and 24th Annual Conference of rehabilitation in MS; 2019

ECTRIMS

Abstract: EP1564Type:Abstract Category: Therapy - Immunomodulation/ImmunosuppressionL.V. Juriol1, N. Valeff1, K. Thiele2, S. Schepansks2, M.S. Ventimiglia1, P. Arck2, J. Correale3, F. Jensen11Laboratory for Immunology of Reproduction, CEFYBO-UBA-CONICET, Caba, Argentina, 2Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 3Department of Neuroimmunology and Demyelinating Diseases, FLENI, Caba, ArgentinaPregnancy has a strong influence on Multiple Sclerosis (MS) reducing the relapse frequencies of the disease. Human chorionic gonadotrophin (hCG) has immunosupresive fuctions and it is only produced during pregnancy.To evaluate the potential immunomodulatory effect of hCG on cytokine production by immune cells in vitro and on clinical sympthoms in-vivo in the context of MS.In-vitro:PBMC were isolated from blood samples of women suffering MS, during fertile life, and cultivated with urinary (u,100IU/ml) or recombinant (r,5ug/ml) hCG or without hCG (c) for 24 h. PMA, Ionomycin and Brefeldin A were added for the last 5h of culture. Cytometric Bead Array was performed to evaluate TNF-α and IL-10 production in supernatants and also Flow cytometry was used to characterize the production of TNF-α and IL-10 by lymphocyte subsets: CD19(B cells), CD3,CD4 (Th cells), CD25,Foxp3(Treg). B cell co-stimulatory molecules were also evaluated(CD86,CD80).In-vivo:Experimental Autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 with MOG35-55 peptide disolved with Complete Freund´s adjuvant and a dose of Pertussis Toxin (PT). Two days later, another dose of PT was injected. hCG treatment began with the EAE induction and a 10 IU hCGu or 0,5 µg of hCGr dose was administered every second day for 16 days. Disease course was evaluated by a Clinical Score.hCG significantly lowered the production of TNF-α in supernatants (pg/ml,c:1969±420; u:1421±427*;r:1061±181*,*p< 0.05vs c) but did not have any effect on IL-10. However, a negative correlation was observed between IL-10 vs Age of the Patient (AP,Pearson r=-0.61*,*p< 0.05) in the context of hCGr. This corelation was also observed in the production of IL-10 by B cells vs AP (Spearman r=-0.77*,*p< 0.03). Intracellular staining showed a reduction in the production of TNF-α by B (MFI,c:133±40;r:106±33*,*p< 0.03vs c) and Th cells (%,c:63±3;r:60±3*,*p< 0.02 vs c) and also an increase in the production of IL-10 by Treg (MFI,c:3.8±0.8;r:3.3±1.2*,*p< 0.03vs c) in the context of hCGr. Furthermore, hCGr reduced the % of co-expressing CD86+CD80+ B cells (c:3.1±0.6;r:2.5±0.4*,*p< 0.001 vs c). During EAE induction, hCGr was able to extend the day of onset of the disease and reduce the Scores during relapse (data were analyzed by paired t-test).Overall, hCG offers a wide spectrum of benefficial effects as a potential therapy for MS. this opens new avenues to further prove its effectiveness and become another tool box to treat MS.