Search for neuron-specific and nonneuron-specific antibodies in narcoleptic patients with and without HLA DQB1*0602.
OBJECTIVE
Narcolepsy is strongly associated with the presence of HLA DQB1*0602. This and other evidence suggests that human narcolepsy is an autoimmune disease. This is in distinction to that found in canine models where hypocretin receptor 2 mutations are etiologic. We decided to test for the presence of several neuron-specific and organ-specific autoantibodies to see if they were present in HLA DQB1*0602-associated or cataplexy-associated narcolepsy or could serve as a serologic marker of the illness.


METHODS
We tested for N-type and P/Q-type voltage-gated calcium-channel antibodies, neuronal nicotinic acetylcholine receptor alpha3 subunit, acetylcholine receptor-binding antibodies, striated muscle antibodies, Type 1 Purkinje cell cytoplasmic antibodies, types 1 and 2 antineuronal nuclear antibodies and amphiphysin antibodies, GAD-65 antibody, and thyroid microsomal and thyroglobulin antibodies in the serum of 43 patients with or without cataplexy, 41 with known HLA status.


METHODS
Narcoleptic subjects were recruited from the Mayo Sleep Disorders Center.


METHODS
N/A.


METHODS
N/A.


RESULTS
No antibody test yielded significantly positive results for the group as a whole or for subgroups of patients with cataplexy or positive HLA DQB1*0602 status.


CONCLUSIONS
These results do not support the hypothesis that narcolepsy is an autoimmune disease. However, it is possible that the autoimmune attack is very selective and does not involve the epitopes measured in this study. Recent findings that the hypocretin neurotransmission system is involved in animal models of narcolepsy should lead to research to look for antibodies directed against components of the hypocretin neurotransmission system in narcolepsy.
Black
John Logan
JL
Department of Psychiatry, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Krahn
Lois E
LE
Pankratz
V Shane
VS
Silber
Michael
M
D000328:Adult; D000906:Antibodies / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins; D009290:Narcolepsy / Q000235:genetics / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000276:immunology*; D064446:Orexin Receptors; D017354:Point Mutation / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000276:immunology; D013954:Thyroglobulin / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C075637:amphiphysin; D013954:Thyroglobulin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2