Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 137; no. 1; pp. 51 - 59
• Main Authors: Villar, Luisa M, Espiño, Mercedes, Cavanillas, María L, Roldán, Ernesto, Urcelay, Elena, de la Concha, Emilio G, Sádaba, Maria C, Arroyo, Rafael, González-Porqué, Pedro, Álvarez-Cermeño, José C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2010; Elsevier
• Subjects: ADP-ribosyl Cyclase 1 - metabolism; Adult; Allergy and Immunology; Antibodies; Antigens, CD19 - metabolism; Autoimmune diseases of the central nervous system; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Biological and medical sciences; Blood Cells - cytology; Blood Cells - immunology; Blood Cells - metabolism; CD5 Antigens - metabolism; Central nervous system; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - immunology; Cerebrospinal Fluid - metabolism; Chemokine CXCL13 - cerebrospinal fluid; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency - genetics; Genotype; Humans; Immunoglobulin G - biosynthesis; Immunoglobulin G - cerebrospinal fluid; Immunoglobulin M - biosynthesis; Immunoglobulin M - cerebrospinal fluid; Immunoglobulin M - immunology; Interleukin-5 - cerebrospinal fluid; Interleukin-6 - cerebrospinal fluid; Lipids - immunology; Male; Medical sciences; Membrane Glycoproteins - metabolism; Multiple sclerosis; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin Sheath - immunology; Neurology; Oligoclonal Bands - biosynthesis; Oligoclonal Bands - cerebrospinal fluid; Oligoclonal Bands - immunology; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Recurrence; Tumor Necrosis Factor-alpha - cerebrospinal fluid; Tumor Necrosis Factor-alpha - genetics; Antibodies; Multiple sclerosis; Autoimmune diseases of the central nervous system; Immunopathology; Nervous system diseases; Immunoglobulins; Antibody; Central nervous system; Autoimmune disease; IgM; Mechanism; Inflammatory disease; Immunology; Central nervous system disease
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2010.06.007

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.