Y. Aladro
Hospital Universitario de Getafe
Neurology

Author Of 4 Presentations

 On-Demand Program
Epidemiology Poster Presentation

LB1166 - Risk and outcomes of COVID-19 in patients with multiple sclerosis in Madrid Spain  (ID 1480)

Speakers
Authors
Presentation Number
LB1166
Presentation Topic
Epidemiology

Abstract

Background

Infections are an important cause of hospitalization in patients with MS. Data on outcomes of COVID-19 in patients with MS are limited

Objectives

To quantify the risks of infection, hospitalization, admission to intensive care and death due to SARS-CoV-2 infection among patients with MS relative to the general population, and to identify factors associated with risk of hospitalization

Methods

A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit (ICU) admission and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison.

Results

Two-hundred nineteen patients with MS were included in the registry, 51 of whom were hospitalized. The infection incidence rate (IR) was lower in patients with MS than the general population (adjusted IR ratio 0.78; 95% confidence interval: 0.70–0.80), but hospitalization rates were higher (adjusted relative risk 6.52 [6.13–7.04]). Disease severity was generally low, with only one ICU admission and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying therapy (DMT) and hospitalization risk.

Conclusions

Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue DMT should be based on a careful risk-benefit assessment.

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0324 - Effect of ocrelizumab treatment in peripheral blood leukocyte subsets of Primary Progressive Multiple Sclerosis patients (ID 1613)

Speakers
Authors
Presentation Number
P0324
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Ocrelizumab is the first drug approved as disease modifying treatment for primary progressive (PP) multiple sclerosis (MS). As a humanized monoclonal antibody targeting CD20 cells, it is widely known that ocrelizumab treatment results in B cells depletion, but less is known about the effects of this drug in other blood leukocyte subsets of PPMS patients.

Objectives

To explore the changes induced by ocrelizumab in blood immune cells of PPMS patients to further understand their effects in the abnormal inflammatory response.

Methods

Multi-centre prospective longitudinal study including fifty‐three PPMS patients who initiated ocrelizumab treatment. Effector, memory, and regulatory cells were analyzed by flow cytometry at baseline and after 6 months of treatment. To assess differences between baseline and after 6 months, Wilcoxon matched paired tests were used and p values were corrected using Bonferroni test.

Results

Ocrelizumab decreased numbers of naïve and memory B cells (p<0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha (p<0.0001 in all cases). A reduction of CD20+ T cell numbers (p=0.02) and percentages (p<0.0001) was also observed. We also detected a clear remodelation of the T cell compartment characterized by relative increases of the naïve/effector ratio in CD4+ (p=0.002) and CD8+ (p=0.002) T cells, and relative decreases of CD4+ (p=0.03) and CD8+ (p=0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p=0.002), with no changes in those producing inflammatory cytokines. All these changes resulted in a reduction of serum neurofilament light chain (sNfL) levels (p=0.009).

Conclusions

Effector B cell depletion by ocrelizumab treatment induces changes in the T cell response of PPMS patients towards a low inflammatory profile. This resulted in a decrease of sNfL levels.

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Pathogenesis – Immunology Poster Presentation

P0964 - Herpesvirus serology in primary progressive multiple sclerosis (ID 919)

Speakers
Authors
Presentation Number
P0964
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Viruses have been involved in multiple sclerosis (MS) in last years. However, almost all of the studies published so far have focused on patients with relapsing-remitting MS (RRMS), with no data about viruses in patients with progressive primary MS (PPMS). Due to the differences that exist between these two forms of MS it would be interesting to know if there is also differences regarding viruses previously related to the etiopathogenesis of the disease.

Objectives

The aim of this study was to analyze the prevalence and titters of different viral antibodies: IgG against EBNA-1 and VCA of Epstein-Barr virus (EBV), IgG and IgM against Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), in PPMS patients and to compare those results with other cohort of RRMS patients.

Methods

A total of 166 MS patients were recruited: 71 with PPMS and 95 with RRMS (mean age: 48 and 43.6 years, respectively; gender: 47.9% and 61% female, respectively). We analyzed the presence and titters of the antibodies above mentioned with ELISA commercial kits, following manufacturer instructions.

Results

1. Herpesvirus prevalences: we only found a statistical significant difference for IgG antibodies against EBNA-1 of EBV (84.5% of PPMS patients were positive vs. 97.8% of RRMS patients; p=0.002). When we analyzed these prevalences by age groups (<45 and >45 years), we only found statistical significant differences between PPMS and RRMS patients under 45 years: 84.6% of PPMS patients were positive for IgG against EBNA-1 vs. 100% of RRMS patients (p=0.015), and 26.9% of PPMS patients were positive for IgM against HHV-6 vs. 7.7% of RRMS patients (p=0.021). 2. Herpesvirus titters: we found that IgG titters against CMV were higher among PPMS patients than in RRMS patients (31.3 AU vs. 16.01 AU, p=0.0001); IgG titters against HHV-6 were also higher in PPMS patients (29.3 AU vs. 20.5, p=0.004); IgG titters against EBNA-1 of EBV were lower in PPMS patients than in RRMS patients (16.4 AU vs. 22.8 AU, p<0.0001).

Conclusions

We have found statistical significant differences between different herpesvirus prevalences and titters between PPMS and RRMS patients that should be deeper studied to evaluate their possible contribution to the existing differences between these two forms of MS.

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Pathogenesis – Immunology Poster Presentation

P0975 - Lipid-specific oligoclonal IgM bands condition age-related changes in multiple sclerosis (ID 1396)

Speakers
Authors
Presentation Number
P0975
Presentation Topic
Pathogenesis – Immunology

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.

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