Analysis for neurodegeneration, T and B cell infiltration in GAD encephalitis

Identifier:  TFG:2140

Handle: https://hdl.handle.net/20.500.11797/TFG2140

Authors:  Verdú de Juan, Laia

Abstract:
In the past years, several types of antibody-associated encephalitis haven been discovered. This group is also named autoimmune epilepsies since patients reveal prominent epileptic seizures. Antibody-associated encephalitis can be classified according to serum antibodies and their specific targets: Antibodies against intracellular antigens, Antibodies to extracellular epitopes, antibodies against intranuclear epitopes and antibodies against neuronal membrane antigens. Glutamic acid decarboxylase (GAD) antibody-associated encephalitis is a type of autoimmune encephalitis with antibodies against intracellular antigens. GAD encephalitis is characterized by the presence of anti- GAD65 antibody in patient’s serum and/or cerebrospinal fluid. Since GAD antibodies target intracellular antigens it is thought that T cell cytotoxicity might be responsible for the neuronal damage. Furthermore, histopathological studies in GAD encephalitis have shown T and B cell infiltration in the hippocampus of patients. More in detail, some patients have shown GrB+ lymphocytes in apposition to single neurons suggesting that these cells might be responsible for the neuronal loss. Thus, in this study this hypothesis has been tested using more cases. In addition, the pathogenic role of anti-GAD antibodies is still unknown since there is no clear evidence that GAD antibodies can bind to GAD65 in situ neurons. In this study it has been hypothesized if there is a loss of GAD65 in the hippocampus of patients with GAD encephalitis. Finally, there are no studies supporting correlation between neuronal loss, T, B and plasma cell infiltration and the disease duration. Here it has been hypothesized if there is actually a correlation between these factors in GAD encephalitis.