Studies on
HLA antigens were conducted in several patient populations with the following findings: (a) All 135 Japanese narcoleptic patients, eight of whom were considered to have "symptomatic"
narcolepsy, were found to be
HLA-DR2 and
HLA-DQw1 positive. All 17 members of a subgroup of the original population were also found to be HLA-Dw2-positive. It was concluded that
HLA-DR2 is a prerequisite for the development of
narcolepsy and that the diagnosis of
narcolepsy can be excluded if
HLA-DR2 or HLA-Dw2 is negative. The distinction between idiopathic and symptomatic
narcolepsy needs to be reconsidered. (b) Haplotype studies in three families with narcoleptic members enabled detection of children at high risk for
narcolepsy. (c) Of the 54 patients with disorders of
excessive daytime sleepiness other than
narcolepsy, those with essential
hypersomnia (EHS) had a higher frequency of HLA-DR2; the others had a lower frequency. The DR2-positive EHS group could include members with an incomplete form of
narcolepsy; the DR2-negative EHS group had disorders essentially different from
narcolepsy, although both positive and negative groups manifested
hypnagogic hallucinations,
sleep paralysis, and sleep onset REMs. Two further studies were conducted in subgroups of the original narcoleptic population studied. In a subgroup of 30 patients who underwent lymphocyte subset studies, no T-cell abnormalities were detected; it is unlikely that an autoimmune mechanism is involved in the development of
narcolepsy. In a subgroup of 33 narcoleptic patients, Southern's blot analysis of
DNA using a DQ beta probe revealed three specific restriction fragments. Further studies are necessary to locate the
DNA locus that carries the susceptibility gene for
narcolepsy.