Evaluate the Evidence for Type 1 Narcolepsy as an AutoimmuneDisorder

Abstract

The presence of cataplexy and the loss of hypocretin neurons manifested as low serum or CSF hypocretin-1 levels distinguish narcolepsy type 1 (NT1) from other types of hypersomnias. Autoimmunity has long been proposed as the pathogenesis for NT1 for its association with HLA-DQB1*06:02 and an increase in incidence after 2009 H1N1 flu pandemic and Pandemrix vaccination. We critically evaluated the evidence through literature search from genetics, cellmediated immunity, and humoral immunity perspectives to verify if NT1 is an autoimmune disease. The strongest evidence is the anti-tribbles homologue 2 (TRIB2) in which both the seroactivity and the loss of hypocretin neurons secondary to this autoantibody were observed, albeit through different studies. Cell-mediated autoimmunity is therefore confirmed. We were only able to identify partial evidence for cytotoxic autoimmunity in causing NT1. Further research is hence needed to explore if the hypocretin neuronal destruction can be due to cytotoxic T cells or other autoantibodies.