Evolution of antibody titres against Epstein-Barr virus and human herpesvirus 6A/B and expression of multiple sclerosis-associated retrovirus in the serum of pregnant multiple sclerosis patients.

Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls-P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.

Cytokine profile during pregnancy predicts relapses during pregnancy and postpartum in multiple sclerosis.

OBJECTIVE: To explore the serum cytokine profile associated with disease activity during pregnancy and postpartum in MS, and to assess any potential biomarkers predicting the occurrence of relapses during this period. METHODS: We included 53 MS pregnant women recruited between 2007 and 2018. Interferon-gamma, Tumor necrosis factor-alpha, interleukin-17, granulocyte/macrophage-colony stimulating factor, Activin-A, interleukin-10, and programmed-death-ligand-1 (PD-L1) were measured quarterly in serum by ELISA. RESULTS: Seventeen patients (32%) experienced relapses during pregnancy or puerperium and 37(68%) did not. We did not found differences in clinical characteristics or treatment status between the two groups. However, relapsing patients showed at the first trimester of pregnancy considerably lower levels of serum Activin-A (336.4 pg/dl [289.6-491.7], median [IQR] vs. 760.0 pg/dl [493.2-1108.0],p = .003), which correlated positively with serum PD-L1 (r = 0.53,p = .0005) and IL-10 (r = 0.43,p = .004) values. Activin-A levels lower than 515 pg/ml at the first trimester identified patients with high probability of relapsing during pregnancy and postpartum (OR = 13.75, CI: 2.5-76.8, p = .001). CONCLUSIONS: MS patients with no relapses during pregnancy and puerperium showed an early triggering of a tolerogenic innate immune response evidenced by high serum Activin-A concentrations during the first trimester of pregnancy. Thus, serum Activin-A can be a useful biomarker to predict clinical activity during this period.