title: Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis.
abstract: We described previously that multiple sclerosis (MS) patients with oligoclonal IgM against myelin lipids (M+) develop an aggressive disease. Our aim was to assess possible mechanisms regulating the production of these antibodies. We studied B cell subsets in 180 patients with MS, and 69 with other neurological diseases. M+ MS patients showed a moderate increase of CD5(+) B-cell percentage in peripheral blood and a considerable augment of these cells in cerebrospinal fluid (CSF) that correlated with intrathecal IgM production. The appearance of CD5(+) B cells into the central nervous system (CNS) was related to increased CXCL13 and TNF-alpha levels in CSF. Moreover, the presence of oligoclonal IgM associated with a SNP at position -376 of the TNF-alpha promoter. These results help to elucidate the B lymphocytes responsible for intrathecal IgM secretion in MS and the origin of this abnormal B-cell response in patients with aggressive MS.
authors.affiliation: Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain. lvillar.hrc@salud.madrid.org
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espiño
authors.forename: María L
authors.initials: ML
authors.lastname: Cavanillas
authors.forename: Ernesto
authors.initials: E
authors.lastname: Roldán
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sádaba
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Pedro
authors.initials: P
authors.lastname: González-Porqué
authors.forename: José C
authors.initials: JC
authors.lastname: Alvarez-Cermeño
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000276:immunology*; D015848:Interleukin-5 / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008055:Lipids / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology; D043025:Oligoclonal Bands / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D018941:Antigens, CD19; D018956:CD5 Antigens; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; C508599:IL5 protein, human; C508600:IL6 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D015850:Interleukin-6; D008055:Lipids; D008562:Membrane Glycoproteins; D043025:Oligoclonal Bands; D014409:Tumor Necrosis Factor-alpha; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1