title: [Identification and characterization of a monoclonal IgM reacting with disialylated gangliosides recognizing the CANOMAD syndrome].
abstract: We reported the laboratory phenotype of a monoclonal IgM-lambda against disialylated gangliosides, in a 81-year-old man admitted to a neurological department because of the progressive development of distal paresthesias, gait unsteadiness, difficulty to walk and having falls. Serological studies revealed an IgM monoclonal protein with lambda light chain component of MGUS type. IgM level was 4 g/L. The positive laboratory studies showed high titers of IgM antibodies in excess of 1/10(5) against specific disialylated gangliosides including GD1b, GD3, GT1b and GQ1b. There was no serum IgM binding to MAG and SGPG/SGLPG. Clonality by in-house immunodot of ganglioside antibodies was demonstrated using kappa and lambda light chain specific antibodies. Light chain subtype of the anti-ganglioside antibody activity and monoclonal IgM was lambda subtype. The reactivity at high titers was against gangliosides containing the disialosyl epitope. The clinical and laboratory features have been described under the acronym CANOMAD: Chronic Ataxic Neuropathy with Ophthalmoplegia, M proteins, cold Agglutinins and Disialosyl antibodies. Administration of IVIg produced a significant neurological improvement during six years. Then the neuropathy became refractory in the IVIg and worsened in severity, a cure by Rituximab® was established. The patient died from a pneumopathy only two months later. Monoclonal IgM binding to disialylated gangliosides have high level of specificity for diagnosis of the CANOMAD syndrome.
authors: Centre de biologie et pathologie Est, Service de neurobiologie, Groupement hospitalier Est, Lyon Bron.
authors: Ismael
authors: I
authors: Boussaïd
authors: Françoise
authors: F
authors: Bouhour
authors: Christophe
authors: C
authors: Vial
authors: Christiane
authors: C
authors: Caudie
mesh_terms: D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001259:Ataxia / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D017809:Fatal Outcome; D020234:Gait Ataxia / Q000209:etiology; D005732:Gangliosides / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009886:Ophthalmoplegia / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D010292:Paresthesia / Q000209:etiology; D010525:Peripheral Nerves / Q000378:metabolism; D000069283:Rituximab; D017211:Treatment Failure
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D005732:Gangliosides; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D019158:N-Acetylneuraminic Acid