Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy

John L. Black, Michael H. Silber, Lois E. Krahn, Rajeswari K. Avula, Denise L. Walker, V. Shane Pankratz, Paul A. Fredrickson, Nancy L. Slocumb

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1 * 0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1 * 0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. Methods: Serum samples of 41 DQB1 * 0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. Results: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. Conclusions: The hypothesis that DQB1 * 0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Original languageEnglish (US)
Pages (from-to)504-509
Number of pages6
JournalBiological psychiatry
Volume58
Issue number6
DOIs
StatePublished - Sep 15 2005

Keywords

  • DQB1*0602
  • Narcolepsy
  • autoimmunity
  • hypocretin
  • immunoglobulin G
  • orexin

ASJC Scopus subject areas

  • Biological Psychiatry

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    Black, J. L., Silber, M. H., Krahn, L. E., Avula, R. K., Walker, D. L., Pankratz, V. S., Fredrickson, P. A., & Slocumb, N. L. (2005). Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy. Biological psychiatry, 58(6), 504-509. https://doi.org/10.1016/j.biopsych.2005.04.026