Neuroimmunology

My team and I actively work at both diagnostic and research levels in the field of paraneoplastic and autoimmune neurological syndromes. A group of encephalopathies has been demonstrated to be mediated by an autoimmune mechanism. The recent discovery of autoantibodies associated with these diseases has changed the diagnostic approach. In particular, onconeural antibodies are associated with paraneoplastic syndromes. In this situation, an extracerebral neoplasm leads to an inflammatory response of the central nervous system (CNS). The most common onconeural antibodies are anti-Hu and anti-Ma2. Different studies have demonstrated that onconeural antibodies should be considered specific biomarkers, whereas the pathogenic mechanism of disease is due to the activation of cytotoxic T lymphocytes. The same pathogenic mechanism is used by the second category of autoantibodies: the intracellular synaptic antigens. An example of this type of antigen are antibodies directed against glutamate decarboxylase (GAD). The third category of antibodies, directed against surface antigens (e.g. NMDA, AMPA, and GABA_B receptors), were identified more recently. They are called Neuronal Surface Antibodies (NsAbs) and are not always associated with tumors. In this case, the pathogenic mechanism is caused by the antibodies themselves which act directly on neuronal cells. Although different antibodies related to neurological autoimmune syndromes have to date been identified, some patients with clinical features of autoimmune encephalopathies still test negative for onconeural, GAD and NbAbs antibodies (“seronegative patients”). Negativity does not necessarily imply the absence of autoantibodies, rather it could simply be that the specific antibody causing the syndrome has not yet been identified.

Medical Diagnostic Activities. My group is recognized at the national level as a reference center for the diagnosis of autoimmune neurological syndromes based on the detection of autoantibodies, in collaboration with the Treviso Hospital. Each year, we receive more than 500 patient samples (both cerebrospinal fluid [CSF] and serum) from all over Italy and screen for the presence of antibodies in both biological fluids to establish the autoimmune etiology of the encephalitis. Moreover, since 2005 our laboratory has been collecting sera and/or CSF from all over Italy from patients defined in the literature as having possible autoimmune encephalopathies.

Research Activities. In order to identify novel antineural biomarkers in “seronegative” patients with suspected autoimmune encephalopathies, we are developing a standardized protocol of indirect immunohistochemistry on fixed rat brain cryosections. This will enable us to study seronegative patients and correlate the clinical information with patterns associated with these novel autoantibodies.

Contact mail: neuroimmunologia@irpcds.org