Author Of 2 Presentations
P0939 - Antibody titters against EBV and HHV-6A/B and expression of MSRV ENV in the serum of pregnant multiple sclerosis patients (ID 1197)
Abstract
Background
Pregnancy is a special period within the clinical course of multiple sclerosis (MS), characterized by a reduction in the relapse rate and slower disease progression. On the contrary, during puerperium, relapse rate increases again. Viruses have been related to the etiopathogenesis of the disease, especially with disease activity.
Objectives
To analyse the serum antibody titters against Epstein-Barr virus (EBV) (EBNA-1 and VCA) and human herpesvirus 6 A/B (HHV-6A/B), as well as the expression of the envelope protein of the MS-associated retrovirus (MSRV ENV) in pregnant MS patients during pregnancy and postpartum. To study their possible relationship with the disease activity during pregnancy and postpartum, as well as their potential role in predicting the risk of relapses.
Methods
Serum samples were collected from 71 pregnant women, 50 with MS and 21 healthy controls, at every trimester of pregnancy and in the postpartum. Antibody titters against the above mentioned viruses were analysed by ELISA commercial kits, following manufacturer instructions; gene expression of MSRV ENV was analysed by qRT-PCR.
Results
IgM titres against HHV-6A/B were higher in MS patients than in healthy controls in the three trimesters of pregnancy and in the postpartum period (U-Mann Whitney): p =0.00001 for the first trimester; p=0.021 for the second trimester; p = 0.000005 for the third trimester; p =0.001, for the postpartum period). Furthermore, IgM titres against HHV-6A/B in the first trimester were higher in patients with relapses (U Mann Whitney, p = 0.052). Regarding the expression of MSRV ENV, the percentage of positivity during the first trimester was significantly higher in MS patients with relapses during pregnancy compared to those who did not (Fisher, p = 0.038).
Conclusions
High IgM titters against HHV-6A/B and the expression of MSRV ENV during the first trimester of pregnancy could act as predictors of relapse risk during pregnancy / postpartum. Although further studies are needed to validate these results, this study support the relation between viruses and relapses in pregnant MS patients.
P0975 - Lipid-specific oligoclonal IgM bands condition age-related changes in multiple sclerosis (ID 1396)
- C. Picón
- A. Tejeda-Velarde
- J. Fernandez-Velasco
- M. Comabella
- R. Alvarez-Lafuente
- E. Quintana
- S. Sainz de la Maza
- E. Monreal
- N. Villarrubia
- J. Álvarez-Cermeño
- M. Domínguez-Mozo
- L. Ramió I Torrentà
- E. Rodríguez-Martin
- E. Roldán
- Y. Aladro
- S. Medina
- M. Espiño
- J. Masjuan
- C. Matute-Blanch
- M. Muñoz-San Martin
- C. Espejo
- C. Guaza
- L. Costa-Frossard
- L. Villar
Abstract
Background
Age has high influence on clinical course of chronic inflammatory diseases such as multiple sclerosis (MS). Lipid-specific oligoclonal IgM bands (LS-OCBM) in cerebrospinal fluid (CSF) of MS patients are biomarkers of high inflammatory disease. However, the relationship between both variables has not been fully studied.
Objectives
To explore age-related changes in CSF of MS patients leading to senescence and to study the role of LS-OCBM in this process.
Methods
A prospective cross-sectional study of 263 MS patients followed at Ramon y Cajal University Hospital, Madrid. Seventy-two showed (M+) and 191 (M-) lacked CSF LS-OCBM. We explored CSF immune cells, soluble mediators, microRNAs and clinical data.
Results
MS patients older than 45 years (O45) showed significant rises in CSF Programmed death ligand 1 (PD-L1; p=0.001) and T-cell immunoglobulin mucin-3 (TIM-3; p<0.0001), which induce lymphocyte tolerance, and in Chitinase 3-like-1 (p<0.0001) and Activin-A (p<0.0001), which lead to innate cell activation. This associated with low values of pro-inflammatory B cells and of Th17 lymphocytes. In addition, M- O45 patients experienced significant increases in miR-125b-5p (p=0.01) and miR-145-5p (p=0.02), two miRNA associated with immune senescence, an increase of let-7b-5p (p=0.01) that counteract innate-cell activation, a dramatic decrease of CSF lymphocytes (p<0.0001) and of NK cells (p=0.002) and increased serum anti-cytomegalovirus antibodies (p=0.009). However, M+ O45 patients exhibited a reduction of miR-204-5p (p=0.01), that induce innate-cell activation and increased CSF levels of superoxide dismutase (p=0.04) and isoprostane (p=0.03), markers of oxidative stress. These changes resulted in increased Multiple Sclerosis Severity Score (MSSS) on M+ O45 patients.
Conclusions
M- O45 MS patients showed inhibition of the intrathecal adaptive immune response and early immunosenescence. Conversely, M+ O45 MS patients displayed intrathecal innate cell activation and accelerated disability worsening. These data could be relevant for treating aged MS patients.