Increased immune complexes of hypocretin autoantibodies in narcolepsy.
BACKGROUND
Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes.


METHODS
Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls.


RESULTS
Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies.


CONCLUSIONS
Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.
Deloumeau
Aude
A
Digestive System and Nutrition Laboratory (ADEN EA 4311), Rouen Institute of Medical Research and Innovation, Rouen University, Rouen, France.
Bayard
Sophie
S
Coquerel
Quentin
Q
Déchelotte
Pierre
P
Bole-Feysot
Christine
C
Carlander
Bertrand
B
Cochen De Cock
Valérie
V
Fetissov
Sergueï O
SO
Dauvilliers
Yves
Y
D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015992:Body Mass Index; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D009290:Narcolepsy / Q000097:blood / Q000276:immunology*; D009479:Neuropeptides / Q000276:immunology*; D000068797:Orexins
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins