Immune-Mediated Nervous System Disease study group

Research Activity

The Neuroimmunology Group focuses on unraveling the role of immunity and inflammation in pediatric-onset epilepsies, encephalopathy with seizures, adult and pediatric paraneoplastic and autoimmune neurological syndromes. The main aims also include the identification of potential diagnostic and prognostic biomarkers that represent fundamental tools in the clinical settings. Our laboratory works in synergy with the clinical work, in particular with the pediatric and adult neurology department of Azienda Ospedale Università Padova (Dr. Margherita Nosadini, Dr. Marco Puthenparampil, Prof. Stefano Sartori, Prof. Paolo Gallo) and the neurobiology laboratory. Moreover, long-standing collaborations have been nurtured with the Multiple Sclerosis Center of the Dept. of Neurology of Vicenza Hospital (Dr. Luigi Zuliani), the Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia (Dr. Matteo Gastaldi), and the Depart. of Pediatric Neurology, Children’s Hospital Datteln, University Witten/Herdecke, Datteln, Germany (Prof. Kevin Rostásy). Our group received funding to support a project on pediatric-onset multiple sclerosis (pedMS). PedMS is an immune demyelinating disorder of childhood characterized by chronic inflammation that leads to progressive brain degeneration. Globally, its incidence and prevalence are about 0.87 per 100,000 individuals annually and 8.11 per 100,000 individuals, respectively. The clinical presentation of PedMS at onset could overlap with recurrent or multiphasic acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), or clinically isolated syndromes. Importantly, some of these disorders are distinct from MS, as their pathogenic mechanism is predominantly antibody-mediated. The most important characterized antigens are present on glial cells: aquaporin-4 (AQP4), a water channel mainly present on astrocytes, is the most important target in NMOSD, Glial Fibrillary Acidic Protein (GFAP) are targeted in a more recently described autoimmune astrocytopathy most frequently presenting as meningoencephalitis, while Myelin Oligodendrocyte Glycoprotein (MOG) is the main target in pediatric ADEM and other syndromes that have clinical-radiological overlap with MS. Up to now, these CNS inflammatory demyelinating disorders and their outcomes are distinguished based on major clinical and radiologic features; however, more reliable biologic markers need to be identified. The aims of our project are: i) the identification of novel imaging and biological markers in children with pedMS; ii) a comprehensive, single-cell multi-omics analysis of the pathogenic cell populations; ii) the identification of possible target antigens, and iii) the identification of novel antigens through T cell receptor (TCR) and HLA profiling; iii) and iii) eventually, the identification of novel therapeutic target molecules. This project is conducted in close collaboration with the “Translational Immunology” Laboratory in IRP directed by Prof. Barbara Molon. The following researchers are actively involved in this shared project: Dr. Alessandra Maria Testa, Dr. Francisca Venegas Celedón, and Dr. Annachiara Marin.

Other ongoing projects of the Neuroimmunology Group include the characterization of GFAP astrocytopathy through a systematic literature review, with focus on clinical-radiological features in children, and the description of the Italian cohorts of pediatric NMDAR encephalitis and MOG associated disorders.