PATHOGENESIS OF IMMUNE-MEDIATED NEURONAL DISORDERS

Principal Investigators

JOSEP DALMAU

ICREA Professor

Syndromes and mechanisms of paraneoplastic and autoimmune encephalitis

ALBERT SAIZ

Neurologist

Neuroimmunology and Multiple Sclerosis

Research team

 

Thais Armangue

Postdoctoral Researcher

 

Pablo Jercog

Postdoctoral Researcher

 

Francesco Mannara

Postdoctoral Researcher

 

Eugenia Maria Martinez

Postdoctoral Researcher

 

Jesus Planaguma

Postdoctoral Researcher

 

Marija Radosevic

Postdoctoral Researcher

 

Anna Garcia

Early Stage Researcher

 

Jon Landa

Early Stage Researcher

 

Estibaliz Maudes

Early Stage Researcher

 

Gemma Olive

Early Stage Researcher

 

Paula Peixoto

Early Stage Researcher

 

Amirpasha Zamani

Early Stage Researcher

 

Ester Aguilar

Technician

 

Mercedes Alba

Technician

 

Eva Maria Caballero

Technician

 

Maria Rodes

Project Manager

 

Myrna Rosenfeld

Others

 

Lidia Sabater

Others

Research Interest

 

This programme is focused on the discovery of autoimmune neurologic diseases, mainly those mediated by antibodies against neuronal cell surface proteins or synaptic receptors. These studies include characterisation of syndromes and diseases; identification of novel antibodies and target autoantigens; and determination of the mechanisms of disease at the behavioural, synaptic, and neuronal circuitry levels. For this, a wide variety of molecular and electrophysiological techniques in vitro and in vivo are used. The resulting findings have led to guidelines on the differential diagnosis and treatment of autoimmune encephalitis, and new concepts on how autoimmunity can affect synaptic function, memory and behaviour.

Technologies & Methods

 

  • Immunohisto- and cytochemistry
  • Electrophysiology
  • Biology
  • Animal Models
  • Advanced Optical Imaging
  • Clinical Neuroimaging
  • Neuropsychological Testing
  • Computational Neuroimmunology
  • In-silico Modeling

Featured Projects

 

    • Análisis multiescala de los autoanticuerpos contra el receptor NMDA en psicosis. . Instituto de Salud Carlos III (ISCIII). AC18/00009. Josep Dalmau

 

    • A Translational Model of Antibody-mediated Synaptic Disease: Symptoms, Neuronal Circuits, and the Mechanisms of Memory Loss and Recovery.. Fundació Caixa de Pensions ‘La Caixa’. HR17-00149. Josep Dalmau

 

    • Biomarcadores de resonancia magnética avanzada en esclerosis múltiple: asociación con el perfil clínico evolutivo y sustrato genético.. Instituto de Salud Carlos III (ISCIII). PI15/00587. Albert Saiz

 

    • Confidential.. Fundació Privada CELLEX. 15/318. Josep Dalmau

 

    • Immune-mediated diseases of the synapse: symptoms, brain networks, and the link to human memory. Instituto de Salud Carlos III (ISCIII). PIE16/00014. Josep Dalmau

 

    • Incorporació del Dr. Jesús Planagumà al grup de recerca del Programa de Neuroimmunologia. Departament de Salut de la Generalitat de Catalunya. SLT002/16/00346. Josep Dalmau

 

    • Investigations in anti-NMDAR encephalitis: New diagnostic test, the role of inflammation in an animal model, and allosteric modulation of NMDAR as a therapeutic strategy. Instituto de Salud Carlos III (ISCIII). PI20/00197. Josep Dalmau

 

    • Red Temática de Investigación Cooperativa en Salud – Esclerosis múltiple. Instituto de Salud Carlos III (ISCIII). RD16/0015/0002

Featured Publications

 

    • Fernández-Velasco, J. I., Kuhle, J., Monreal, E., Meca-Lallana, V., Meca-Lallana, J., Izquierdo, G., Gascón-Giménez, F., Sainz de la Maza, S., Walo-Delgado, P. E., Maceski, A., Rodríguez-Martín, E., Roldán, E., Villarrubia, N., Saiz, A., Blanco, Y., Sánchez, P., Carreón-Guarnizo, E., Aladro, Y., Brieva, L., … Villar, L. M. (2021). Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS. Neurology – Neuroimmunology Neuroinflammation, 8(2), e940. https://doi.org/10.1212/NXI.0000000000000940

 

    • Yeh, W. Z., Widyastuti, P. A., Van der Walt, A., Stankovich, J., Havrdova, E., Horakova, D., Vodehnalova, K., Ozakbas, S., Eichau, S., Duquette, P., Kalincik, T., Patti, F., Boz, C., Terzi, M., Yamout, B. I., Lechner-Scott, J., Sola, P., Skibina, O. G., Barnett, M., Onofrj, M., … MSBase Study Group (2021). Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis. Neurology, 10.1212/WNL.0000000000012084. Advance online publication. https://doi.org/10.1212/WNL.0000000000012084

 

    • Capuano, R., Zubizarreta, I., Alba-Arbalat, S., Sepulveda, M., Sola-Valls, N., Pulido-Valdeolivas, I., Andorra, M., Martinez-Heras, E., Solana, E., Lopez-Soley, E., Montejo, C., Blanco, Y., Fernández-Velasco, J. I., Gallo, A., Bisecco, A., Villoslada, P., Saiz, A., Llufriu, S., Villar, L. M., & Martinez-Lapiscina, E. H. (2021). Oligoclonal IgM bands in the cerebrospinal fluid of patients with relapsing MS to inform long-term MS disability. Multiple Sclerosis (Houndmills, Basingstoke, England), 1352458520981910. Advance online publication. https://doi.org/10.1177/1352458520981910

 

    • Mannara, F., Radosevic, M., Planagumà, J., Soto, D., Aguilar, E., García-Serra, A., Maudes, E., Pedreño, M., Paul, S., Doherty, J., Quirk, M., Dai, J., Gasull, X., Lewis, M., & Dalmau, J. (2020). Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis. Brain, 143(9), 2709–2720. https://doi.org/10.1093/brain/awaa195

 

    • Armangue, T., Olivé-Cirera, G., Martínez-Hernandez, E., Sepulveda, M., Ruiz-Garcia, R., Muñoz-Batista, M., Ariño, H., González-Álvarez, V., Felipe-Rucián, A., Jesús Martínez-González, M., Cantarín-Extremera, V., Concepción Miranda-Herrero, M., Monge-Galindo, L., Tomás-Vila, M., Miravet, E., Málaga, I., Arrambide, G., Auger, C., Tintoré, M., … Villar-Vera, C. (2020). Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. The Lancet. Neurology, 19(3), 234–246. https://doi.org/10.1016/S1474-4422(19)30488-0

 

    • Spatola, M., Petit Pedrol, M., Maudes, E., Simabukuro, M., Muñiz-Castrillo, S., Pinto, A. L., Wandinger, K. P., Spiegler, J., Schramm, P., Dutra, L. A., Iorio, R., Kornblum, C., Bien, C. G., Höftberger, R., Leypoldt, F., Titulaer, M. J., Sillevis Smitt, P., Honnorat, J., Rosenfeld, M. R., Graus, F., … Dalmau, J. (2020). Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis. Neurology, 95(22), e3012–e3025. https://doi.org/10.1212/WNL.0000000000010854

 

    • Martinez-Hernandez, E., Guasp, M., García-Serra, A., Maudes, E., Ariño, H., Sepulveda, M., Armangué, T., Ramos, A. P., Ben-Hur, T., Iizuka, T., Saiz, A., Graus, F., & Dalmau, J. (2020). Clinical significance of anti-NMDAR concurrent with glial or neuronal surface antibodies. Neurology, 94(22), e2302–e2310. https://doi.org/10.1212/WNL.0000000000009239

 

    • Landa, J., Gaig, C., Plagumà, J., Saiz, A., Antonell, A., Sanchez-Valle, R., Dalmau, J., Graus, F., & Sabater, L. (2020). Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration. Annals of Neurology, 88(5), 1023–1027. https://doi.org/10.1002/ana.25857

 

 

    • Carceles-Cordon, M., Mannara, F., Aguilar, E., Castellanos, A., Planagumà, J., & Dalmau, J. (2020). NMDAR Antibodies Alter Dopamine Receptors and Cause Psychotic Behavior in Mice. Annals of Neurology, 88(3), 603–613. https://doi.org/10.1002/ana.25829

 

    • Matute, C., Palma, A., Serrano-Regal, M. P., Maudes, E., Barman, S., Sánchez-Gómez, M. V., Domercq, M., Goebels, N., & Dalmau, J. (2020). N-Methyl-D-Aspartate Receptor Antibodies in Autoimmune Encephalopathy Alter Oligodendrocyte Function. Annals of Neurology, 87(5), 670–676. https://doi.org/https://doi.org/10.1002/ana.25699

 

    • Joubert, B., García-Serra, A., Planagumà, J., Martínez-Hernandez, E., Kraft, A., Palm, F., Iizuka, T., Honnorat, J., Leypoldt, F., Graus, F., & Dalmau, J. (2020). Pregnancy outcomes in anti-NMDA receptor encephalitis. Neurology – Neuroimmunology Neuroinflammation, 7(3), e668. https://doi.org/10.1212/NXI.0000000000000668

 

    • Paolilo, R. B., Hacohen, Y., Yazbeck, E., Armangue, T., Bruijstens, A., Lechner, C., Apostolos-Pereira, S. L., Martynenko, Y., Breu, M., de Medeiros Rimkus, C., Wassmer, E., Baumann, M., Papetti, L., Capobianco, M., Kornek, B., Rostásy, K., da Paz, J. A., Ciccarelli, O., Lim, M., … Deiva, K. (2020). Treatment and outcome of aquaporin-4 antibody–positive NMOSD. Neurology – Neuroimmunology Neuroinflammation, 7(5), e837. https://doi.org/10.1212/NXI.0000000000000837

 

    • Sepulveda M, Delgado-García G, Blanco Y, Sola-Valls N, Martinez-Lapiscina EH, Armangué T, Montejo C, Pulido-Valdeolivas I, Martinez-Hernandez E, Ariño H, Escudero D, Ruiz-García R, Llufriu S, Dalmau J, Graus F, Saiz A. (2019). Late-onset neuromyelitis optica spectrum disorder: The importance of autoantibody serostatus. Neurology-Neuroimmunology & Neuroinflammation. 6:6, 2019

 

    • Yamamura T., Kleiter I., Fujihara K., Palace J., Greenberg B., Zakrzewska-Pniewska B., Patti F., Tsai C., Saiz A., Yamazaki H., Kawata Y., Wright P., De Seze J. (2019). Trial of satralizumab in neuromyelitis optica spectrum disorder. New England Journal of Medicine, 381(22):2114-2124, 2019

 

 

    • Armangue, T., Spatola, M., Vlagea, A., Mattozzi, S., Cárceles-Cordon, M., Martinez-Heras, E., Llufriu, S., Muchart, J., Erro, M. E., Abraira, L., Moris, G., Monros-Giménez, L., Corral-Corral, Í., Montejo, C., Toledo, M., Bataller, L., Secondi, G., Ariño, H., Martínez-Hernández, E., … Zabalza, A. (2018). Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. The Lancet Neurology, 17(9), 760–772. https://doi.org/10.1016/S1474-4422(18)30244-8

 

    • Petit-Pedrol, M., Sell, J., Planagumà, J., Mannara, F., Radosevic, M., Haselmann, H., Ceanga, M., Sabater, L., Spatola, M., Soto, D., Gasull, X., Dalmau, J., & Geis, C. (2018). LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory. Brain, 141(11), 3144–3159. https://doi.org/10.1093/brain/awy253

Knowledge transfer & Innovation

 

  • Diagnostic method for detecting a new form of autoimmune encephalitis and related subject-matter (DPPX). Licensed to Euroimmun, Inc. USA Patent Number: US 9,719,993 B2. European patent application number: 12183919.5. Josep Dalmau
  • Diagnosis of a neurologic disease (IgLON5). Licensed to Euroimmun, Inc. EP2905622A1. Josep Dalmau i Francesc Graus
  • Methods and compositions for treatment and diagnosis of autoimmune encephalitis or epilepsy (NMDAR test). Licensed to Euroimmun, Inc, Germany. USA Patent Number: US 7,972,796. European patent number: EP 2 057 466. Canadian patent number: 2,697,742. Josep Dalmau, Myrna R Rosenfeld i David R Lynch
  • Methods for diagnosing and treating encephalitis or epilepsy (GABAB autoantibody test). Licensed to Euroimmun, Inc. USA Patent Number: US 8,685,656. European Patent Number: 2483417. Josep Dalmau