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VOLUME 28, ISSUE 04


Analysis of Hypocretin (Orexin) Antibodies in Patients with Narcolepsy

John L. Black, III, MD1,2; Michael H. Silber, MBChB3; Lois E. Krahn, MD4; Paul A. Fredrickson, MD5; V. Shane Pankratz, PhD6; Rajeswari Avula1; Denise L. Walker1; Nancy L. Slocumb3

1Psychogenomics Laboratory, 2Department of Psychiatry and Psychology; 3Mayo Sleep Disorders Center and Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN; 4Department of Psychiatry and Psychology and Mayo Sleep Disorders Laboratory, Mayo Clinic College of Medicine, Scottsdale, AZ; 5Mayo Sleep Disorders Laboratory, Mayo Clinic College of Medicine, Jacksonville, FL; 6Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN



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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.

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