Analysis of hypocretin (orexin) antibodies in patients with narcolepsy

Sleep. 2005 Apr;28(4):427-31. doi: 10.1093/sleep/28.4.427.


Study objectives: We tested the hypothesis that patients with narcolepsy have serum antibodies specific for preprohypocretin and its derivatives.

Design: We tested sera from strictly diagnosed HLA DQB1*0602-positive narcoleptic patients with cataplexy for evidence of autoantibodies against human preprohypocretin, hypocretin 1 and 2, N-terminal leader and C-terminal peptides of preprohypocretin using enzyme-linked immunosorbent assays (ELISA). These results were compared to samples from nonnarcoleptic psychiatric and sleep apnea controls. Laboratory personnel were blinded to subject status.

Setting: Narcoleptic patients and nonnarcoleptic controls were recruited from the Mayo Clinic facilities in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. Laboratory testing was conducted in the Mayo Psychogenomic Laboratory at the Rochester Mayo Clinic.

Participants: A sample of 34 narcoleptic patients and 49 nonnarcoleptic controls.

Interventions: None.

Measurements and results: ELISA measurements were in optical density. Primary analyses were of the entire narcoleptic and control groups for each potential antigen, and none of the differences reached P values required for significance after Bonferroni adjustment. Secondary analyses by age and sex yielded P values that were significant after Bonferroni adjustment in only 2 cases, but further statistical analyses cast doubt on the veracity of these differences. In all cases where a significant difference was recorded, the hypothesis was not supported because the control optical density reading was higher than the narcoleptic values.

Conclusions: These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies / immunology*
  • Brain / immunology
  • Brain / pathology
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology*
  • HLA-DQ beta-Chains
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Middle Aged
  • Narcolepsy / genetics
  • Narcolepsy / immunology*
  • Narcolepsy / pathology
  • Neuropeptides / genetics
  • Neuropeptides / immunology*
  • Orexins
  • Polymerase Chain Reaction
  • Synaptic Transmission / physiology


  • Autoantibodies
  • DNA Primers
  • HCRT protein, human
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins