title: Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS.
abstract: Oligoclonal IgM bands restricted to cerebrospinal fluid are an unfavorable prognostic marker in MS, the most common demyelinating disease of the CNS. We have attempted to identify the B cell subpopulation responsible for oligoclonal IgM secretion and the specificity of these bands. In addition, we explored the relationship between specificity and disease evolution. Intrathecal B cell subpopulations present in 29 MS patients with oligoclonal IgM bands and 52 without them were analyzed. A considerable increase in CD5(+) B lymphocytes was found in patients with oligoclonal IgM bands. These cells mostly secrete IgM antibodies recognizing nonproteic molecules. We also studied whether oligoclonal IgM bands present in cerebrospinal fluid of 53 MS patients were directed against myelin lipids. This was the case in most patients, with phosphatidylcholine being the most frequently recognized lipid. Disease course of 15 patients with oligoclonal IgM against myelin lipids and 33 patients lacking them was followed. Patients with anti-lipid IgM suffered a second relapse earlier, had more relapses, and showed increased disability compared with those without anti-lipid IgM. The presence of intrathecal anti-myelin lipid IgM antibodies is therefore a very accurate predictor of aggressive evolution in MS.
authors.affiliation: Departments of Immunology and Neurology, Hospital Ramón y Cajal, Madrid, Spain. lvillar.hrc@salud.madrid.org
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.forename: María C
authors.initials: MC
authors.lastname: Sádaba
authors.forename: Ernesto
authors.initials: E
authors.lastname: Roldán
authors.forename: Jaime
authors.initials: J
authors.lastname: Masjuan
authors.forename: Pedro
authors.initials: P
authors.lastname: González-Porqué
authors.forename: Noelia
authors.initials: N
authors.lastname: Villarrubia
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espiño
authors.forename: José A
authors.initials: JA
authors.lastname: García-Trujillo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Bootello
authors.forename: José C
authors.initials: JC
authors.lastname: Alvarez-Cermeño
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D016130:Immunophenotyping; D008055:Lipids / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000737:chemistry* / Q000276:immunology*; D043025:Oligoclonal Bands / Q000096:biosynthesis* / Q000276:immunology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D007075:Immunoglobulin M; D008055:Lipids; D043025:Oligoclonal Bands