Narcolepsy and the HLA region

Narcolepsy was first shown to be tightly associated with HLA-DR2 and DQ1 in 1983, suggesting a possible autoimmune mechanism. Early investigations fai led to demonstrate this hypothesis, postulating that HLA-DR2 was only a lin kage marker for another, unknown narcolepsy-causing gene. The autoimmune hy pothesis is now being re-evaluated under the light of recent results. Like many other autoimmune disorders, narcolepsy usually starts during adolescen ce, is human leukocyte antigen (HLA)-associated, multigenic and environment ally influenced. Furthermore, HLA-association studies indicated a primary H LA-DQ effect with complex HLA class II allele interactions and a partial co ntribution of HLA to overall genetic susceptibility. Finally, recent result suggests that human narcolepsy is associated with the destruction of a sma ll number of hypothalamic neurons containing the peptide hypocretins (orexi ns). This data is consistent with an immune destruction of hypocretin-conta ining cells as the most common etiology for human narcolepsy. (C) 2001 Else vier Science B.V. All rights reserved.