Pathophysiological factors in the diagnosis and treatment of the Guillain-Barre syndromes

The immunological drivers of the demyelinating form of Guillain-Barre syndrome (GBS) and the mechanisms of secondary axonal degeneration are little understood. Similarly the pathological progression of axonal GBS is incomplete, and neuroprotection strategies are unstudied. Emerging variants, including Zika-GBS, remain entirely uncharted. We hypothesise that humoral immunity to nerve antigens drives GBS. More specifically, and based on our existing data, that the predilection for demyelinating versus axonal GBS is governed by the cell-type specificity of anti-glycolipid antibodies. Herein we will interrogate newly gathered GBS biobanks (notably IGOS) for nerve antibody targets, focusing on lipid complexes using locally-developed glycoarray technology, and then determine their suitability as biomarkers for different GBS variants. Our pathogenesis studies on demyelinating GBS will focus on targeting glial GM1 and sulphatide with unique monoclonal antibodies, developed in house, using newly developed mice in which the paranodal myelin can be specifically targeted. We will use these models to understand pathomechanisms of myelin and axonal injury and repair, and test new therapeutic pathways, notably related to complement activation and calcium influx that are ripe for rapid clinical translation. Our overall goal is to change the GBS landscape for future patients, health care providers and researchers.