Event Details:
Selina Yogeshwar is a graduate student from the Mignot lab. She will present her work on HLA association in anti-IgLON5 Disease.
Anti-IgLON5 disease is a rare, but likely underdiagnosed type of autoantibody encephalitis with a heterogeneous clinical phenotype, including sleep disturbances, movement disorders and brainstem dysfunction. Its pathophysiology is still elusive, although a dominant association with HLA-DRB1*10:01 and HLA-DQB1*05:01 strongly supports an autoimmune basis. While previous studies suggested that autoimmunity is mediated via HLA-DR, we hypothesise that this disease is in fact mediated via HLA-DQ instead. Our results from the, so far, largest genetic study in the field support a rank-wise association of three distinct HLA-DQ5 molecules. Further, we suspect autoimmunity is mediated against a post-translationally modified form of IgLON5, in line with reduced T cell priming against these epitopes. Our research has important implications for understanding the pathophysiology underlying this condition and paves the path for new treatment strategies for this devastating and oftentimes lethal condition. Furthermore, anti-IgLON5 disease is a compelling example of autoimmune-driven neurodegeneration, raising important questions and implications for general brain resilience and the pathophysiology underlying tauopathies.