Intractable hiccup and nausea in Neuromyelitis optica: a clinical predictor of acute spinal exacerbations.

LUCIANA MELAMUD; VALERIA RIVAROLA; JUAN FERNADEZ; CLAUDIA CAPURRO; ANDRES VILLA

Gothenburg, Suiza

Congreso; European Committee of Treatment and Research in Multiple Sclerosis, ECTRIMS 2010; 2010

ECTRIM

Anti-Aquaporin 4 antibodies present in patients with Neuromyelitis Optica reduces the water permeability of astrocytes plasma membrane Luciana Melamud1-2, Juan M Fernández1,Valeria Rivarola1, Claudia Capurro1 and Andrés Villa2 1Laboratorio de Biomembranas, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. 1Laboratorio de Biomembranas, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. 1-2, Juan M Fernández1,Valeria Rivarola1, Claudia Capurro1 and Andrés Villa2 1Laboratorio de Biomembranas, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. Laboratorio de Biomembranas, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Argentina.2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Ramos Mejía, Buenos Aires, Argentina. 2Servicio de Neurología, Hospital General de Agudos Ramos Mejía, Buenos Aires, Argentina. Background: NMO-IgG autoantibody is now considered a useful serum biomarker of neuromyelitis optica (NMO). A series of clinical and pathological observations suggest that NMO-IgG may play a central role in NMO physiopathology. Objective: The aim of this in vitro-based study was to characterize molecular and functional consequences of interaction between NMO-IgG and astrocytes primary cultures. Methods: Three NMO-IgG positive NMO patients from Neuroimmunology of the Ramos Mejia Hospital, Argentina were selected. As control, we included serum from 3 NMO-IgG negative healthy controls. Primary cultures of rat astrocytes were incubated with heat-inactivated control or NMO patients’ sera (dilution 1/50), for 1 h at 4ºC or 12 h at 37ºC and then immunofluorescence studies as well as water permeability measurements by fluorescence videomicroscopy were performed. Fluorescence was quantified by densitometric analysis using Image-J software. Results: Immunofluorescence studies showed that cells exposition to NMO patients´ sera for 1 h at 4°C (to restrict membrane fluidity) resulted in IgG binding to the plasma membrane in a linear pattern that colocalized with AQP4, while serum IgG from controls did not bind significantly. In contrast, after exposure for 12 h at 37°C, NMO patients’ sera containing AQP4 specific IgG resulted in disappearance of AQP4 fluorescence from the plasma membrane while control sera had no effect on AQP4 expression. Even more, 1 h exposition of astrocytes to NMO-IgG does not change the water permeability, indicating that the water pore is not affected by the binding of IgG, but 12 h of exposition to NMO-IgG clearly induced a significant reduction of the water permeability (time constant of water transport, t. (s), control vs. NMO-IgG sera 18.04 ±1.04 vs. 34.96 ± 4.45, p < 0.01). 0.01). t. (s), control vs. NMO-IgG sera 18.04 ±1.04 vs. 34.96 ± 4.45, p < 0.01). Conclusions: NMO patients´sera IgG has a selective pathogenic effect on cell membranes expressing AQP4. We demonstrated that NMO-IgG binding to astrocytes alters AQP4 expression and decreases permeability.