Pathogenesis of Immune-Mediated Neuronal Disorders

Experimental Neurology

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.

Principal Investigators

Josep Dalmau

Full Professor

Yolanda Blanco

Full Professor

Technologies & Methods

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

Research Team

Thais Armangue

Postdoctoral Researcher

Eugenia Maria Martinez

Postdoctoral Researcher

Jesus Planaguma

Postdoctoral Researcher

Estibaliz Maudes

Early Stage Researcher

Gemma Olive

Early Stage Researcher

Ester Aguilar

Technician

Mercedes Alba

Technician

Eva Maria Caballero

Technician

Maria Rodes

Project Manager

Myrna Rosenfeld

Others

Lidia Sabater

Others

Victor Patricio

Early Stage Researcher

Laura Marmolejo

Early Stage Researcher

Mar Guasp

Postdoctoral Researcher

Marianna Spatola

ICREA Researcher

AnaBeatriz Araujo Gama Serafim

Early StageResearcher

Selected publications

Alba-Arbalat, S., Solana, E., Lopez-Soley, E., Camos-Carreras, A., Martinez-Heras, E., Vivó, F., Pulido-Valdeolivas, I., Andorra, M., Sepulveda, M., Cabrera, J. M., Fonseca, E., Calvi, A., Alcubierre, R., Dotti-Boada, M., Saiz, A., Martinez-Lapiscina, E. H., Villoslada, P., Blanco, Y., Sanchez-Dalmau, B., & Llufriu, S. (2023). Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry, jnnp-2023-332332. https://doi.org/10.1136/jnnp-2023-332332

Armangué, T., Olivé-Cirera, G., Martínez-Hernandez, E., Rodes, M., Peris-Sempere, V., Guasp, M., Ruiz, R., Palou, E., González, A., Marcos, M. Á., Erro, M. E., Bataller, L., Corral-Corral, Í., Planagumà, J., Caballero, E., Vlagea, A., Chen, J., Bastard, P., Materna, M., … Dalmau, J. (2023). Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies. Brain, 146(10), 4306–4319. https://doi.org/10.1093/brain/awad238

Banwell, B., Bennett, J. L., Marignier, R., Kim, H. J., Brilot, F., Flanagan, E. P., Ramanathan, S., Waters, P., Tenembaum, S., Graves, J. S., Chitnis, T., Brandt, A. U., Hemingway, C., Neuteboom, R., Pandit, L., Reindl, M., Saiz, A., Sato, D. K., Rostasy, K., … Palace, J. (2023). Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. The Lancet Neurology, 22(3), 268–282. https://doi.org/10.1016/S1474-4422(22)00431-8

Blanco, Y., Escudero, D., Lleixà, C., Llufriu, S., Egri, N., García, R. R., Alba, M., Aguilar, E., Artola, M., Aldea Novo, M., Alvarez, S., Caballero, E., Cabrera-Maqueda, J. M., Fonseca, E., Guasp, M., Hernando, A., Martinez-Hernandez, E., Olivé-Cirera, G., Lopez-Contreras, J., … Saiz, A. (2023). mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis. Neurology Neuroimmunology & Neuroinflammation, 10(6). https://doi.org/10.1212/NXI.0000000000200163

Ceanga, M., Rahmati, V., Haselmann, H., Schmidl, L., Hunter, D., Brauer, A.-K., Liebscher, S., Kreye, J., Prüss, H., Groc, L., Hallermann, S., Dalmau, J., Ori, A., Heckmann, M., & Geis, C. (2023). Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony. Cell Reports, 42(10), 113166. https://doi.org/10.1016/j.celrep.2023.113166

Chen, L.-W., Guasp, M., Olivé-Cirera, G., Martínez-Hernandez, E., Ruiz García, R., Naranjo, L., Saiz, A., Armangue, T., & Dalmau, J. (2024). Antibody Investigations in 2,750 Children With Suspected Autoimmune Encephalitis. Neurology Neuroimmunology & Neuroinflammation, 11(1). https://doi.org/10.1212/NXI.0000000000200182

Dalmau, J., & Graus, F. (2023). Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease. The Lancet Neurology, 22(6), 529–540. https://doi.org/10.1016/S1474-4422(23)00083-2

Fonseca, E., Cabrera-Maqueda, J. M., Ruiz-García, R., Naranjo, L., Diaz-Pedroche, C., Velasco, R., Macias-Gómez, A., Milisenda, J. C., Muñoz-Farjas, E., Pascual-Goñi, E., Gállego Perez-Larraya, J., Saiz, A., Dalmau, J., Blanco, Y., Graus, F., Martinez-Hernandez, E., Aldecoa, I., Barcelo, M. I., Canneti, B., … Tagliani, P. (2023). Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study. The Lancet Neurology, 22(12), 1150–1159. https://doi.org/10.1016/S1474-4422(23)00335-6

Gövert, F., Abrante, L., Becktepe, J., Balint, B., Ganos, C., Hofstadt-van Oy, U., Krogias, C., Varley, J., Irani, S. R., Paneva, S., Titulaer, M. J., de Vries, J. M., Boon, A. J. W., Schreurs, M. W. J., Joubert, B., Honnorat, J., Vogrig, A., Ariño, H., Sabater, L., … Leypoldt, F. (2023). Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis. Brain, 146(2), 657–667. https://doi.org/10.1093/brain/awac276

Guasp, M., Rosa-Justicia, M., Muñoz-Lopetegi, A., Martinez-Hernandez, E., Armangue, T., Sugranyes, G., Stein, H., Prades, L., Ariño, H., Planagumà, J., De La Serna, E., Escudero, D., Llufriu, S., Sánchez-Valle, R., Santamaria, J., Compte, A., Castro-Fornieles, J., & Dalmau, J. (2023). Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders (S22.006). Neurology, 100(17_supplement_2). https://doi.org/10.1212/WNL.0000000000202506

Kalincik, T., Sharmin, S., Roos, I., Freedman, M. S., Atkins, H., Burman, J., Massey, J., Sutton, I., Withers, B., Macdonell, R., Grigg, A., Torkildsen, Ø., Bo, L., Lehmann, A. K., Havrdova, E. K., Krasulova, E., Trněný, M., Kozak, T., van der Walt, A., … Kermode, A. (2023). Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis. JAMA Neurology, 80(7), 702. https://doi.org/10.1001/jamaneurol.2023.1184

Landa, J., Serafim, A. B., Gaig, C., Saiz, A., Koneczny, I., Hoftberger, R., Santamaria, J., Dalmau, J., Graus, F., & Sabater, L. (2023). Patients’ IgLON5 autoantibodies interfere with IgLON5-protein interactions. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1151574

Martinez-Heras, E., Solana, E., Vivó, F., Lopez-Soley, E., Calvi, A., Alba-Arbalat, S., Schoonheim, M. M., Strijbis, E. M., Vrenken, H., Barkhof, F., Rocca, M. A., Filippi, M., Pagani, E., Groppa, S., Fleischer, V., Dineen, R. A., Bellenberg, B., Lukas, C., Pareto, D., … Llufriu, S. (2023). Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes. Journal of Neurology, Neurosurgery & Psychiatry, 94(11), 916–923. https://doi.org/10.1136/jnnp-2023-331531