The focus of our work is to identify new disorders, develop biomarkers, and uncover mechanisms of disease in autoimmune and paraneoplastic encephalitis, a group of neuro-inflammatory disorders characterized by highly specific immune responses against neuronal cell surface and synaptic proteins.
This work includes the identification of immune mechanisms associated with autoimmune encephalitis and the development of diagnostic tests. We aim to elucidate how infections and tumors can trigger autoimmune encephalitis and to uncover other triggers of these disorders. Clinical studies are focused in understanding how autoimmune encephalitis affect cognition and memory in patients using imaging, neurophysiologic, serologic, and neuropsychological testing in order to guide rehabilitation strategies and accelerate recovery. At a basic level we are developing models of autoimmune encephalitis in vitro, in vivo and in silico, and are using these models to test therapeutic and preventative strategies as well as to elucidate how the immune responses associated with autoimmune encephalitis affect brain function (e.g., memory and learning) at the level of the synapse and brain circuits. Results of these studies have had an impact on many different medical and neuroscience disciplines, providing a link between immunological processes and neuronal functions involved in memory, behavior, psychosis, epilepsy and neuronal degeneration.
Research Interest
The principal objective of the group is the study of autoimmune/inflammatory brain diseases including autoimmune encephalitis and paraneoplastic neurologic disorders among others. We aim to identify novel biologic, genetic, immunologic, and neuroimaging biomarkers that will allow for early and accurate disease diagnoses and have prognostic value. Studies are also aimed at elucidating the underlying immunopathogenic disease mechanisms through studies that link immunological processes to neuronal dysfunction.
Current Research Line
- Determine the frequency and spectrum of symptoms of each of the known autoimmune encephalitis which will facilitate diagnosis and treatment.
- Identify novel autoimmune encephalitis syndromes and the associated immune responses and target antigens.
- Identify co-morbidities of autoimmune encephalitis and characterize the pathogenic mechanisms leading to the co-morbidities with the goal of prevention and improved treatment of both disorders.
- Elucidate the optimal treatment of each autoimmune encephalitis syndrome and develop guidelines.
- To elucidate biomarkers to predict better outcome and guide personalized medical care of patients with autoimmune encephalitis.
- Elucidate sex and/or gender differences in the autoimmune encephalitis.
- Build outcome models to develop measures of propensity to disease, disease activity, relapses, and treatment response.
- Determine the effects of patients’ immune responses on synaptic function and apply findings in animal models.
- Study how neuronal circuits underlie memory and behavior using state of the art imaging technology applied in health and disease conditions.
Technologies/Methods
- Immunohisto- and cytochemistry
- Electrophysiology
- Molecular Biology
- Animal Models
- Advanced Optical Imaging
- Clinical Neuroimaging
- Neuropsychological Testing
- Computational Neuroimmunology
- In-silico Modeling
Highlighted Publications
Geis C, Planaguma J, Carreño M, Graus F, Dalmau J. Autoimmune Seizures and Epilepsy. J Clin Invest, in press.
Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med 2018;378:840-851.
Armangue T, Spatola M, Vlagea A, Mattozzi S, Cárceles-Cordon M, Martinez-Heras E, Llufriu S, Muchart J, Erro ME, Abraira L, Moris G, Monros-Giménez L, Corral-Corral I, Montejo C, Toledo M, Bataller L, Secondi G, Ariño H, Martínez-Hernández E, Juan M, Marcos MA, Alsina L, Saiz A, Rosenfeld MR, Graus F, Dalmau J. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 2018;17:760-772.
Petit-Pedrol M, Sell J, Planagumà J, MannaraF, Radosevic M, Haselmann H, Ceanga M, Sabater L, Spatola M, Soto D, Gasull X, Dalmau J*, Geis C. LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity, and memory. Brain 2018;141:3144-3159. (*Corresponding author)
Ladépêche L, Planagumà J, Thakur S, Suárez I, Hara M, Borbely J, Sandoval A, Laparra-Cuervo L, Dalmau J,* Lakadamyali M.* Anti-NMDA receptor encephalitis antibodies lead to a subunit specific nanoscale redistribution of NMDA receptors. Cell Reports 2018;23:3759–3768. (*Corresponding authors)