PATHOGENESIS OF IMMUNE-MEDIATED NEURONAL DISORDERS

Principal Investigators

JOSEP DALMAU

ICREA Researcher

Syndromes and mechanisms of paraneoplastic and autoimmune encephalitis

ALBERT SAIZ

Neurologist

Neuroimmunology and Multiple Sclerosis

Research team

 

Francesco Mannara

Postdoctoral Researcher

 

Eugenia Maria Martinez

Postdoctoral Researcher

 

Jesus Planaguma

Postdoctoral Researcher

 

Marija Radosevic

Postdoctoral Researcher

 

Estibaliz Maudes

Early Stage Researcher

 

Gemma Olive

Early Stage Researcher

 

Paula Peixoto

Early Stage Researcher

 

Amirpasha Zamani

Early Stage Researcher

 

Jon Landa

Early Stage Researcher

 

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

Active Projects

 

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

 

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

 

    • Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER). Ministerio de Economia y Competitividad. CB15/00010. Josep Dalmau.

 

    • Contratos Juan Rodés. Ministerio de Sanidad y Consumo. JR17/00012. Josep Dalmau.

 

    • European Committe for treatment & research in múltiple sclerosis. ECTRIMS_20_CTFP_01. Albert Saiz.

 

    • Eficàcia i efectes adversos neurològics de la vacunació contra la COVID-19 en pacients immunodeprimits per l’esclerosi múltiple. Fundació La Marató de TV3. 202132-30. Albert Saiz.

 

    • Investigaciones en la encefalitis anti-NMDAR: nuevo test diagnóstico, papel de la inflamación en un modelo animal, y modulación alostérica de NMDAR como estrategia terapéutica. Ministerio de Ciencia, Innovación y Universidades. PI20/00197. Josep Dalmau.

 

    • Subclinical activity in anti-LGI1 encephalitis: diagnostic test and prognostic implications. Autoimmune Encephalitis Alliance. AEA_CSG_20_01. Josep Dalmau.

 

    • 19 Confidential agreements.

Selected Publications

 

    • Balint, B., Bhatia, K. P., & Dalmau, J. (2021). “Antibody of Unknown Significance” (AUS): The Issue of Interpreting Antibody Test Results. Movement Disorders: Official Journal of the Movement Disorder Society, 36(7), 1543–1547. https://doi.org/10.1002/mds.28597

 

    • Beghi, E., Michael, B. D., Solomon, T., Westenberg, E., Winkler, A. S., & COVID-19 Neuro Research Coalition (2021). Approaches to understanding COVID-19 and its neurological associations. Annals of Neurology, 89(6), 1059–1067. https://doi.org/10.1002/ana.26076

 

    • Comabella, M., Sastre-Garriga, J., Borras, E., Villar, L. M., Saiz, A., Martínez-Yélamos, S., García-Merino, J. A., Pinteac, R., Fissolo, N., Sánchez López, A. J., Costa-Frossard, L., Blanco, Y., Llufriu, S., Vidal-Jordana, A., Sabidó, E., & Montalban, X. (2021). CSF Chitinase 3-Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis. Neurology Neuroimmunology & Neuroinflammation, 8(6), e1082. https://doi.org/10.1212/NXI.0000000000001082

 

    • Dalmau, J., & Martinez-Hernandez, E. (2021). Author Response: Clinical Significance of Anti-NMDAR Concurrent With Glial or Neuronal Surface Antibodies. Neurology, 96(4), 188–189. https://doi.org/10.1212/WNL.0000000000011359

 

    • Gaig, C., Compta, Y., Heidbreder, A., Marti, M. J., Titulaer, M. J., Crijnen, Y., Högl, B., Lewerenz, J., Erro, M. E., Garcia-Monco, J. C., Nigro, P., Tambasco, N., Patalong-Ogiewa, M., Erdler, M., Macher, S., Berger-Sieczkowski, E., Höftberger, R., Geis, C., Hutterer, M., Milán-Tomás, A., … Graus, F. (2021). Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease. Neurology, 97(14), e1367–e1381. https://doi.org/10.1212/WNL.0000000000012639

 

    • Graus, F., Vogrig, A., Muñiz-Castrillo, S., Antoine, J.-C. G., Desestret, V., Dubey, D., Giometto, B., Irani, S. R., Joubert, B., Leypoldt, F., McKeon, A., Prüss, H., Psimaras, D., Thomas, L., Titulaer, M. J., Vedeler, C. A., Verschuuren, J. J., Dalmau, J., & Honnorat, J. (2021). Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurology, Neuroimmunology Neuroinflammation, 8(4). https://doi.org/10.1212/NXI.0000000000001014

 

    • Guasp, M., Giné-Servén, E., Maudes, E., Rosa-Justicia, M., Martínez-Hernández, E., Boix-Quintana, E., Bioque, M., Casado, V., Módena-Ouarzi, Y., Guanyabens, N., Muriana, D., Sugranyes, G., Pacchiarotti, I., Davi-Loscos, E., Torres-Rivas, C., Ríos, J., Sabater, L., Saiz, A., Graus, F., … Dalmau, J. (2021). Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis. Neurology, 97(1), e61 LP-e75. https://doi.org/10.1212/WNL.0000000000012191

 

    • Landa, J., Guasp, M., Míguez-Cabello, F., Guimarães, J., Mishima, T., Oda, F., Zipp, F., Krajinovic, V., Fuhr, P., Honnorat, J., Titulaer, M., Simabukuro, M., Planagumà, J., Martínez-Hernández, E., Armangué, T., Saiz, A., Gasull, X., Soto, D., Graus, F., Sabater, L., … GluK2 encephalitis study group (2021). Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2. Annals of Neurology, 90(1), 101–117. https://doi.org/10.1002/ana.26098

 

    • Nosadini, M., Eyre, M., Molteni, E., Thomas, T., Irani, S. R., Dalmau, J., Dale, R. C., Lim, M., International NMDAR Antibody Encephalitis Consensus Group, Anlar, B., Armangue, T., Benseler, S., Cellucci, T., Deiva, K., Gallentine, W., Gombolay, G., Gorman, M. P., Hacohen, Y., Jiang, Y., Lim, B. C., … Yeshokumar, A. K. (2021). Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis. JAMA Neurology, 78(11), 1333–1344. https://doi.org/10.1001/jamaneurol.2021.3188

 

    • Nosadini, M., Thomas, T., Eyre, M., Anlar, B., Armangue, T., Benseler, S. M., Cellucci, T., Deiva, K., Gallentine, W., Gombolay, G., Gorman, M. P., Hacohen, Y., Jiang, Y., Lim, B. C., Muscal, E., Ndondo, A., Neuteboom, R., Rostásy, K., Sakuma, H., Sharma, S., … Dale, R. C. (2021). International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis. Neurology Neuroimmunology & Neuroinflammation, 8(5), e1052. https://doi.org/10.1212/NXI.0000000000001052

 

    • Papp, V., Magyari, M., Aktas, O., Berger, T., Broadley, S. A., Cabre, P., Jacob, A., Kira, J. I., Leite, M. I., Marignier, R., Miyamoto, K., Palace, J., Saiz, A., Sepulveda, M., Sveinsson, O., & Illes, Z. (2021). Worldwide Incidence and Prevalence of Neuromyelitis Optica: A Systematic Review. Neurology, 96(2), 59–77. https://doi.org/10.1212/WNL.0000000000011153

 

    • Petit-Pedrol, M., Guasp, M., Armangue, T., Lavarino, C., Morales La Madrid, A., Saiz, A., Graus, F., & Dalmau, J. (2021). Absence of GluD2 Antibodies in Patients With Opsoclonus-Myoclonus Syndrome. Neurology, 96(7), e1082–e1087. https://doi.org/10.1212/WNL.0000000000011410

 

    • Schanda, K., Peschl, P., Lerch, M., Seebacher, B., Mindorf, S., Ritter, N., Probst, M., Hegen, H., Di Pauli, F., Wendel, E.- M., Lechner, C., Baumann, M., Mariotto, S., Ferrari, S., Saiz, A., Farrell, M., Leite, M. I. S., Irani, S. R., Palace, J., … Reindl, M. (2021). Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases. Neurology, – Neuroimmunology Neuroinflammation, 8(5). https://doi.org/10.1212/NXI.0000000000001027

 

    • Sarmiento-Monroy, J. C., Espinosa, G., Londoño, M. C., Meira, F., Caballol, B., Llufriu, S., Carrasco, J. L., Moll-Udina, A., Quintana, L. F., Giavedoni, P., Ramírez, J., Inciarte-Mundo, J., Solana, E., Blanco, Y., Martinez-Hernandez, E., Sepúlveda, M., Llorenç, V., Prieto-González, S., Espígol-Frigolé, G., Milisenda, J. C., … Immunocovid Clinic (2021). A multidisciplinary registry of patients with autoimmune and immune-mediated diseases with symptomatic COVID-19 from a single center. Journal of Autoimmunity, 117, 102580. https://doi.org/10.1016/j.jaut.2020.102580

 

    • 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, 96(24), e2989–e3002. https://doi.org/10.1212/WNL.0000000000012084

 

    • Zrzavy, T., Endmayr, V., Bauer, J., Macher, S., Mossaheb, N., Schwaiger, C., Ricken, G., Winklehner, M., Glatter, S., Breu, M., Wimmer, I., Kovacs, G. G., Risser, D. U., Klupp, N., Simonitsch- Klupp, I., Roetzer, T., Rommer, P., Berger, T., Gelpi, E., Lassmann, H., … Höftberger, R. (2021). Neuropathological Variability within a Spectrum of NMDAR-Encephalitis. Annals of Neurology, 90(5), 725–737. https://doi.org/10.1002/ana.26223

Knowledge transfer & Innovation

 

  • Diagnosis of a neurologic disease. AVCRI233-E. Josep Dalmau, Francesc Graus