Neuroimmunology

The Neuroimmunology Laboratory focuses on unraveling the role of immunity and inflammation in pediatric onset epilepsies, encephalopathy with seizures, adult paraneoplastic and autoimmune neurological syndromes. The laboratory actively works at both diagnostic and research levels. The major aims are the identification of possible diagnostic and prognostic biomarkers that are fundamental tools in the clinical settings. We are one of the few national reference centers research laboratories for the diagnosis of this type of neurological diseases.

Medical Diagnostic Activities
Each year, we receive pediatric and adult patients’ samples (both CSF and serum) from all over Italy. The expertise of the laboratory, acquired over the years, and the collective experience in international laboratories, enable us to accurately diagnose pediatric and adult autoimmune neurological syndromes based on the detection of autoantibodies. Our laboratory works in synergy with the clinic, in particular with the pediatric and adult neurology department of Azienda Ospedale Università Padova, the neurobiology laboratory and the Dept. of neurology of Vicenza Hospital (Dr. Luigi Zuliani) and monthly we guarantee the analysis and diagnosis for samples of patients suspected having autoimmune neurological syndromes. We are also reference laboratory for second opinion and doubtful cases for Euroimmun Italy, a diagnostic company, leader in the neuroimmunology field and located here in IRP, too.
We can guarantee the accurate screening and detection of antibodies direct to intracellular protein (e.g. Hu, Yo, Ma2, CV2/CRMP5, Ri, amphiphysin, GAD), surface neuronal antigens (NMDAR, CASPR2, LGI1. GABAb, DPPX) and glia targets (e.g. AQP4, MOG). The presence of antibodies in both the serum and cerebrospinal fluid (CSF) of patients is reached using different techniques such as: indirect immunochemistry, indirect immunofluorescence, immunoblot and cell-based assay (CBA).
Regarding the spectrum of autoimmune neurological disorders, despite the increasing spectrum of antibody reactivity already described, some subjects affected by suspected autoimmune encephalopathies (AE) still test negative for onconeural, GAD and NsAbs (i.e. “seronegative” autoimmune encephalitis patients). This negativity does not necessarily imply the absence of antibody markers, rather possible novel uncharacterized auto-antibodies. Further studies are thus warranted to find new antigens related to the immunological response in neurological patients with possible autoimmune disorders. Based on this hypothesis, our idea is to identify new proteins responsible for the autoimmune response in “seronegative” patients and to investigate the prevalent pathogenic mechanisms and possibly the pathways activated by antibodies.
Furthermore, our group received fundings to support a project regarding Pediatric 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 (Yan K. et al., 2020). PedMS clinical presentation at onset could overlap with recurrent or multiphasic acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), 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. Acquaporin-4 (AQP4), a water channel mainly present on astrocytes, is the most important target in NMO, while Myelin Oligodendrocyte Glycoprotein (MOG) is the main target in pediatric ADEM and other syndromes that 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) to identify novel imaging and biological markers in pedMS children; ii) to understand the type of immune cells involved in the pathogenesis of this disease and iii) eventually find novel therapeutic target molecules.

Contact mail: neuroimmunologia@irpcds.org