NARCOLEPSY AND IMMUNITY

Narcolepsy is a neurological disorder known to be associated with huma n leukocyte antigen (HLA)-DQB1 0602 in humans. In a canine model, the disorder is also genetically linked to a gene of high homology with t he human mu-switch-like immunoglobulin (Ig) gene (current LOD score 13 .6 at 0% recombination). Since association with HLA or other immune fu nction polymorphic genes (T cell receptor of Ig, mainly) is a hallmark of most autoimmune diseases, it is proposed that autoimmunity may als o play a role in the development of narcolepsy. Arguments for and agai nst this hypothesis are reviewed. It is shown that both on the basis o f the most recent molecular studies, and because of some of its clinic al features, narcolepsy may be an autoimmune disorder. However, neithe r systemic nor central nervous system (CNS) evidence of any autoimmune abnormality have ever been found. To reconcile this discrepancy, it i s suggested that the pathological immune process involved in narcoleps y could be difficult to detect because it is restricted to a very smal l region of the brain or targets a low abundance neuroeffector. Altern atively, it is possible that a more fundamental relationship is involv ed between sleep generation and immune regulation. The pathophysiology of narcolepsy may then involve new CNS-immune mechanisms that may she d new light on the sleep process itself.