Perelman School of Medicine at the University of Pennsylvania

Center for Autoimmune Neurology

Research

The Center for Autoimmune Neurology is a true translational research group, where patients have the opportunity to directly benefit from laboratory and clinical research happening now at Penn Medicine.  Current lab studies are focused on what causes the production of these antibodies and the specific ways in which they affect the brain.  Additionally, we are constantly collecting and analyzing epidemiologic data of patients to better pinpoint risk factors and recovery factors, which ultimately leads to improvements in patient care. 

Clinical Research

We are studying how these disease affect patients.  There are many questions to be answered.  For instance, what factors trigger the disease to start? What symptoms are most common in the different groups of patients?  What predicts whether a patient may have a relapse?  What are the best treatments at the different stages of disease?  These questions guide our clinical areas of focus, which include treatment protocols, long-term patient outcomes, patterns of recovery, the importance of antibody titers, predictors or relapses, and development of a clinical rating scale for these diseases. 

New Antibodies

We continue to work on finding new types of autoantibodies that cause autoimmune brain diseases.  Since 2009 we have discovered new antibodies at a rate of approximately 2 per year.  In our research lab we screen patient samples for signs that they have antibodies of the brain, and then work to find what the targets could be.  We combine this lab work with analysis of clinical information to characterize the symptoms associated with each new antibody discovery. 

Mechanisms of Disease

Our group has done important work on learning how antibodies to the NDMAR and other synaptic proteins cause disease.  The antibodies have direct effects of these brain proteins at synapses, tiny areas where nerve cells contact and signal each other.  The new synaptic autoimmune autoantibodies each target a different protein and may each work in different ways. 

Tissue Banking

Much of our research is built around tissue banking patient samples and clinical information.  If your physician suspects that you might have an autoimmune neurological disorder and has ordered antibody tests for you through the Hospital of the University of Pennsylvania's clinical pathology laboratory, then you are eligible to participate in this tissue bank.  Participants in this study will have their clinical information, including their neurologic symptoms, treatments, and recovery information stored in our database to find out more about patterns of these diseases.  We will also store leftover CSF samples from the clinical pathology lab to find out more about these antibodies.  As a participant you may also choose to allow our research findings to be shared with your physician, however it is important to note these are not clinical diagnostic tests, and these findings will not be used to make decisions on your clinical care.  For more information, please contact our Lindsey McCracken at 215-746-8511 or by email

Download a copy of the consent form here.

 

Support Our Work

Much of our research is grant funded, and therefore our progress is dependent on government funding.  Financial contributions from patients and loved ones allow us to expand research goals and focus more heavily on disease discovery, treatment, and patient outcomes.  If you are interested in supporting our work, please contact Lindsey McCracken at 215-746-8511. 

 

Media

Dr. Eric Lancaster addresses the uses and misues of titers in autoimmune encephalitis

Dr. Josep Dalmau addresses the importance of acknowledging the roles of autoimmune an paraneoplastic pathways in the management of epilepsy disorders

 

Select Publications

NMDA:

Planagumà, Jesús, et al. "Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice." Brain 138.1 (2015): 94-109.
 
Armangue, Thaís, et al. "Herpes simplex virus encephalitis is a trigger of brain autoimmunity." Annals of neurology 75.2 (2014): 317-323.
 
Gresa-Arribas, Nuria, et al. "Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study." The Lancet Neurology 13.2 (2014): 167-177.
 
Titulaer, Maarten J., et al. "Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study." The Lancet Neurology 12.2 (2013): 157-165.
 
Dalmau, Josep, et al. "Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis." The Lancet Neurology 10.1 (2011): 63-74.
 
Hughes, Ethan G., et al. "Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis." The Journal of Neuroscience 30.17 (2010): 5866-5875.
 
Dalmau, Josep, et al. "Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies." The Lancet Neurology 7.12 (2008): 1091-1098.

 

Other:

Greene, Maxwell, et al. "Antibodies to Delta/Notch-like Epidermal Growth Factor–Related Receptor in Patients With Anti-Tr, Paraneoplastic Cerebellar Degeneration, and Hodgkin Lymphoma." JAMA neurology 71.8 (2014): 1003-1008

Petit-Pedrol, Mar, et al. "Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABA A receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies." The Lancet Neurology 13.3 (2014): 276-286.

McKeon, Andrew, et al. "Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype." JAMA neurology 70.1 (2013): 44-50.

Lancaster, Eric, and Josep Dalmau. "Neuronal autoantigens—pathogenesis, associated disorders and antibody testing." Nature Reviews Neurology 8.7 (2012): 380-390.

Armangue, Thaís, Mar Petit-Pedrol, and Josep Dalmau. "Autoimmune encephalitis in children." Journal of child neurology 27.11 (2012): 1460-1469.

Lancaster, Eric, et al. "Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia." Annals of neurology 69.2 (2011): 303-311.

Lancaster, E., et al. "Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome." Neurology 77.18 (2011): 1698-1701.

Lancaster, Eric, Eugenia Martinez-Hernandez, and Josep Dalmau. "Encephalitis and antibodies to synaptic and neuronal cell surface proteins." Neurology 77.2 (2011): 179-189.

Lancaster, Eric, et al. "Antibodies to the GABA B receptor in limbic encephalitis with seizures: case series and characterisation of the antigen." The Lancet Neurology 9.1 (2010): 67-76.

Lai, Meizan, et al. "Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series." The Lancet Neurology 9.8 (2010): 776-785.

Moscato, Emilia H., et al. "Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies." European Journal of Neuroscience 32.2 (2010): 298-309.

Lai, Meizan, et al. "AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location." Annals of neurology 65.4 (2009): 424-434.