Amandine Mathias1, Guillaume Perriard1, Mathieu Canales1, Charlotte Soneson2, Mauro Delorenzi3, Myriam Schluep4, Renaud A Du Pasquier5. 1. Laboratory of Neuroimmunology, Neuroscience Research Centre, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. 2. Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. 3. Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland/Ludwig Center for Cancer Research and Department of Oncology, University of Lausanne, Lausanne, Switzerland. 4. Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. 5. Laboratory of Neuroimmunology, Neuroscience Research Centre, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland/Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland.
Abstract
BACKGROUND: Multiple sclerosis (MS) is thought to be T cell mediated but the mechanisms eliciting such a dysregulated adaptative immune response remain enigmatic. OBJECTIVE: To examine the activation profile of antigen-presenting cells (APCs) in MS. METHODS: A total of 98 study subjects were enrolled including patients suffering from relapsing-remitting, secondary- and primary-progressive (PP) MS, other inflammatory neurological diseases, and healthy controls. Blood monocytes and B cells were stimulated using specific ligands of toll-like receptors (TLRs) or inflammasomes or Epstein-Barr virus (EBV) particles. Their activation profile was determined before or after stimulation by flow cytometry (CD40, CD80, CD83, CD86, and human leukocyte antigen-antigen D related (HLA-DR)) and Luminex assay, measuring the concentration of eight cytokines in culture supernatants. Differences among groups were assessed in a linear model framework. RESULTS: We demonstrate that relapsing MS patients exhibit an increased expression of HLA-DR and CD40 ex vivo, mostly at the surface of B cells. Specific stimulations of TLR or inflammasomes enhance the expression of components of the immunological synapse and the cytokine secretion but without differences between categories of study subjects. CONCLUSION: These data suggest that the activation profile of B cells is increased in MS. However, the perception of the danger signal by B lymphocytes and monocytes does not seem to be different in MS patients as compared to control subjects.
BACKGROUND:Multiple sclerosis (MS) is thought to be T cell mediated but the mechanisms eliciting such a dysregulated adaptative immune response remain enigmatic. OBJECTIVE: To examine the activation profile of antigen-presenting cells (APCs) in MS. METHODS: A total of 98 study subjects were enrolled including patients suffering from relapsing-remitting, secondary- and primary-progressive (PP) MS, other inflammatory neurological diseases, and healthy controls. Blood monocytes and B cells were stimulated using specific ligands of toll-like receptors (TLRs) or inflammasomes or Epstein-Barr virus (EBV) particles. Their activation profile was determined before or after stimulation by flow cytometry (CD40, CD80, CD83, CD86, and human leukocyte antigen-antigen D related (HLA-DR)) and Luminex assay, measuring the concentration of eight cytokines in culture supernatants. Differences among groups were assessed in a linear model framework. RESULTS: We demonstrate that relapsing MSpatients exhibit an increased expression of HLA-DR and CD40 ex vivo, mostly at the surface of B cells. Specific stimulations of TLR or inflammasomes enhance the expression of components of the immunological synapse and the cytokine secretion but without differences between categories of study subjects. CONCLUSION: These data suggest that the activation profile of B cells is increased in MS. However, the perception of the danger signal by B lymphocytes and monocytes does not seem to be different in MSpatients as compared to control subjects.
Authors: Michael Zhong; Anneke van der Walt; Maria Pia Campagna; Jim Stankovich; Helmut Butzkueven; Vilija Jokubaitis Journal: Neurotherapeutics Date: 2020-10-14 Impact factor: 7.620