AI Article Synopsis
- Canine and murine models of narcolepsy show mutations linked to hypocretin genes, while human narcolepsy with cataplexy correlates with specific immune system markers (DQB1*0602) and low hypocretin levels, hinting at autoimmune factors.
- A study analyzed serum and cerebrospinal fluid (CSF) samples from narcoleptic and control subjects to identify IgG reactions to preprohypocretin and its cleavage products using several testing methods.
- Results found no significant IgG reactions to preprohypocretin in narcoleptic subjects, contradicting the original hypothesis that these individuals would show such immune responses.
Article 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.
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| http://dx.doi.org/10.1016/j.biopsych.2005.04.026 | DOI Listing |
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