Author Of 2 Presentations
P0324 - Effect of ocrelizumab treatment in peripheral blood leukocyte subsets of Primary Progressive Multiple Sclerosis patients (ID 1613)
- J. Fernandez-Velasco
- J. Kuhle
- E. Monreal
- V. Meca-Lallana
- J. Meca-Lallana
- G. Izquierdo
- F. Gascón Giménez
- S. Sainz de la Maza
- P. Walo Delgado
- A. Maceski
- E. Rodríguez-Martin
- E. Roldán
- N. Villarrubia
- A. Saiz
- Y. Blanco
- P. Sánchez
- E. Carreón Guarnizo
- Y. Aladro
- L. Brieva
- C. Íñiguez
- I. González-Suárez
- L. Rodríguez De Antonio
- J. Masjuan
- L. Costa-Frossard
- L. Villar
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.
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.