Nocturnal Sleep and Daytime Sleepiness in Normal Subjects with HLA - DQB 1 * 0602 NORMAL SUBJECTS

nism underlying narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep, remains elusive, one of the susceptibility factor, HLADQB1*0602, has now been identified. Subjects homozygous or heterozygous for this HLA-DQB1 allele are at much greater risk of developing narcolepsy than subjects without this antigen. DNA sequencing studies, family studies and transethnic association studies have all shown that DQB1*0602, rather than a yet unidentified gene or the previously identified HLA-DR2 subtype, is the actual susceptibility factor for narcolepsy. HLA-DQB1*0602 is present in 90%-100% of narcoleptic patients with definite cataplexy versus 25% in control Caucasian Americans, 38% in control African Americans and 12% in Japanese control subjects. The observation that most narcoleptic patients share specific HLA alleles (e.g., HLA-DQB1*0602 and the associated HLA-DR2 subtype) suggests that the disorder may be autoimmune in nature. Most of the studies conducted to date however rather argue against this possibility. Narcolepsy is not associated with peripheral immune abnormalities and pathological examination of the central nervous system has not revealed any obvious inflammatory lesions in patients with narcolepsy. In a canine model of narcolepsy where the disorder is transmitted as an autosomal recessive trait, reciprocal bone marrow transplantation was also shown not to have transmitted the disorder. Other experiments however favor an autoimmune basis for narcolepsy. Like many autoimmune disorders, predisposition to human narcolepsy involves specific HLA alleles, non HLA genes, and environmental factors. Recent experiments have also shown that the onset narcolepsy-cataplexy is associated with diffuse increased microglial HLA Class II expression in the white matter and neuronal