title: Intrathecal lipid-specific oligoclonal IgM synthesis associates with retinal axonal loss in multiple sclerosis.
abstract: It has been suggested that autoantibodies may induce axonal damage in multiple sclerosis (MS). Optical coherence tomography (OCT) showed that thinning of peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer/inner plexiform (GCIPL) measurements reflect axonal loss in the disease. We investigated whether the intrathecal synthesis of lipid-specific oligoclonal IgM bands (LS-OCMB) associates with thinning of these structures in MS patients.
  
  
  
  58 consecutive MS patients and 70 age-matched healthy controls were assessed. LS-OCMB was studied in cerebrospinal fluid by isoelectric focusing and immunoblotting. RNFL and GCIPL imaging were quantified by spectral domain OCT.
  
  
  
  RNFL and GCIPL were significantly reduced in MS patients compared to controls (p<0.01). RNFL thickness was further reduced in LS-OCMB positive MS patients compared to LS-OCMB negative MS subjects mainly in papillomacular bundle (p<0.05), temporal and inferior quadrants (p<0.05) and inferotemporal sector (p=0.01).
  
  
  
  The presence of LS-OCMB associates with increased retinal axonal loss in MS. This reinforces the relationship found between the intrathecal synthesis of IgM and the axonal damage observed in immunological and pathological studies even in normal-appearing white matter. OCT seems an optimal tool to monitor axonal damage in LS-OCMB positive patients, relevant for therapeutic decisions and quantification of the effects of new neuroprotective treatments.
authors.affiliation: Department of Neurology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain. Electronic address: josecarlos.alvarez@salud.madrid.org.
authors.forename: José C
authors.initials: JC
authors.lastname: Álvarez-Cermeño
authors.affiliation: Department of Ophthalmology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Muñoz-Negrete
authors.affiliation: Department of Neurology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Costa-Frossard
authors.affiliation: Department of Neurology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Sainz de la Maza
authors.affiliation: Department of Immunology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Department of Neurology, Multiple Sclerosis Unit, Ramón y Cajal University Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Rebolleda
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D003430:Cross-Sectional Studies; D006801:Humans; D007075:Immunoglobulin M / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid*; D012160:Retina / Q000473:pathology; D055351:Retinal Neurons / Q000473:pathology*; D066127:White Matter / Q000276:immunology / Q000473:pathology
chemical_list: D007075:Immunoglobulin M; D043025:Oligoclonal Bands
keywords: Axonal loss; IgM; Multiple sclerosis; Neurodegeneration; OCT; Oligoclonal bands