Author Of 2 Presentations
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.
P1138 - short-chain fatty acid during pregnancy in multiple sclerosis: a prospective cohort study (ID 1801)
Abstract
Background
Objective: Pregnancy reduces the annualized relapse rate (ARR) in multiple sclerosis (MS). However it is temporarily increased at puerperium. The exact mechanism underlying this clinical observation remains unknown.
Objectives
We aimed to explore the changes of the short-chain fatty acids (SCFAs) profiles in MS patients and healthy women (HCW) during pregnancy, and to assess any potential biomarker predicting the appearance of relapses during pregnancy and postpartum.
Methods
Methods: We included 53 pregnant MS patients and 21 HCW followed at Hospital Universitario Gregorio Marañón between 2007 and 2018. Patients were evaluated at every trimester of pregnancy and in the puerperium. Serum SCFAs were measured by liquid chromatography-mass spectrometry
Results
Results: Seventeen patients (32%) experienced relapses during pregnancy or puerperium (ACT group) and 37(68%) did not (NO-ACT group). We did not found differences in clinical characteristics or treatment status between the two groups. We observed differences in the SCFAs profile between ACT:NO-ACT groups during pregnancy and puerperium. Acetate levels were higher during the pregnancy-puerperium period in MS patients, regardless of clinical activity, compared to HCW (p: 0.0001). Interestingly, levels of propionate and butyrate below 1,985 μM (1,283 - 3.55) and 0.515 μM (0.01-2.943) respectively during the first trimester were associated with relapses during the pregnancy-puerperium period (p: 0.0001). The ACT group had a lower ratio of propionate/acetate and butyrate/acetate during pregnancy compared to NO-ACT group (<0.0001). The ROC curve showed that a propionate/acetate ratio of 0.36 (AUC 0.96, sensitivity 94%, specificity 92%;) has an OR=165 [CI: 10.2-239.4], p <0.0001) to predict relapses during pregnancy-puerperium.
Conclusions
Conclusions: SCFA levels during pregnancy may be associated with clinical activity in MS, and that their measurement could be useful in predicting the occurrence of relapses during this pregnancy-puerperium period