Project description:We performed gene expression profiling on paired cerebrospinal fluid (CSF) and peripheral blood lymphocyte (PBL) samples from 26 Multiple sclerosis patients without immunomodulatory treatment sampled in relapse or in remission, and 18 controls with other non-inflammatory neurological disorders using Human Genome U133 plus 2.0 arrays (Affymetrix).
Project description:This data set contains the mass spectrometry raw files for the paper The B Cell Repertoire in Multiple Sclerosis Reveals Molecular Mimicry between EBNA1 and GlialCAM. In multiple sclerosis (MS) intrathecal B lymphocytes are directly involved in inflammation and secrete oligoclonal immunoglobulin. However, our understanding of their phenotype, function, and antigen-specificity in MS is incomplete. Molecular mimicry to viruses and self-antigens could be a trigger of autoimmunity. Here we describe phenotypic differences of B cells in blood and cerebro-spinal fluid (CSF) and predominantly implicate plasmablasts in MS pathogenesis. Single-cell paired-chain antibody repertoire sequencing in blood and CSF suggests ongoing intrathecal somatic hypermutation and antigen-specific clonal expansion of intrathecal plasmablasts. The presence of these antibodies was verified using mass spectrometry sequencing of the IgGs isolated from CSF. Selected CSF-derived antibodies were tested against a spectrum of viruses implicated in MS pathogenesis. Antibody MS39p2w174 binds Epstein-Barr Virus (EBV) transcription factor EBNA1 and cross-reacts to the glial cellular adhesion molecule GlialCAM, which is facilitated by serine-phosphorylation. EBNA1 peptide immunization aggravates the mouse model of MS. EBNA1-GlialCAM cross-reactive antibodies are more prevalent in MS patients than in healthy controls. Together, our results suggest that anti-EBNA1- antibodies cross-react with GlialCAM and contribute to MS pathology. This dataset contains the RAW files for the CSF isolated IgGs.
Project description:The identification of target antigens recognized by monoclonal antibodies that have been derived from oligoclonal band IgG of CSF samples from multiple sclerosis patients.
Project description:Multiple myeloma is hematologic malignancies result from clonal proliferation of plasma cells. Recently, increasing evidence supports the hypothesis that microenvironment cells play important roles in the proliferation, survival, and drug resistance of clonal plasma cells. The aim of this study is to culture stromal cells from bone marrow aspirates of patients with multiple myeloma, and to investigate expression profiles of bone marrow stromal cells and their relationships with the clinical characteristics of patients.
Project description:Objective: To investigate how anti-CD20 B cell-depleting monoclonal antibodies (ɑCD20 mAb) alter the composition and gene expression of immune cells in meningeal ectopic lymphoid tissue (mELT) and the CSF in a murine model of Multiple Sclerosis (MS). Methods: We utilized a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in Multiple Sclerosis (MS). We studied the changes in cell composition and gene expression after anti-CD20 treatment in mELT and CSF.
Project description:Multiple myeloma is hematologic malignancies result from clonal proliferation of plasma cells. Recently, increasing evidence supports the hypothesis that microenvironment cells play important roles in the proliferation, survival, and drug resistance of clonal plasma cells. The aim of this study is to culture stromal cells from bone marrow aspirates of patients with multiple myeloma, and to investigate expression profiles of bone marrow stromal cells and their relationships with the clinical characteristics of patients. RNA was extracted cultured bone marrow stromal cells from 15 patients with plasma cell neoplasms, and bone marrow stromal cells from 13 control patients with 9 B-cell lymphoma patients with no evidence of BM involvement and 4 patients with mild-to-moderate cytopenia without evidence of hematologic malignancies
Project description:Tertiary lymphoid structures are reported in the meninges of patients with multiple sclerosis, especially at the progressive stage and are strongly associated to cortical lesions and disability. Besides B cells, these structures comprise follicular helper T cells (Tfh) that are crucial to support B cell differentiation. Tfh play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases but very few is known in multiple sclerosis. Here we reporter transcriptomic profile of CSF infiltrating Tfh compared with paired blood in RRMS patients.
Project description:We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing.
