title: Antibodies Against Hypocretin Receptor 2 Are Rare in Narcolepsy.
abstract: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay.
  
  
  
  Sera from 50 narcolepsy type 1 (NT1) and 11 narcolepsy type 2 (NT2) patients, 22 patients with other sleep disorders, 15 healthy controls, and 93 disease controls were studied. Cerebrospinal fluid (CSFs) from three narcoleptic patients were subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients' sera for 1 hr at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently labeled secondary antibodies to human immunoglobulin G (IgG) and the different IgG subclasses. A nonlinear visual scoring system was used from 0 to 4; samples scoring ≥1 were considered positive.
  
  
  
  Only 3 (5%) of 61 patients showed a score ≥1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40-1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient, and an NT1 patient with normal hypocretin CSF levels.
  
  
  
  Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3 of 61 patients with narcolepsy, although only 1 presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination.
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Giannoccaro
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.|IRCCS Institute of the Neurological Sciences of Bologna, Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pizza
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.|IRCCS Institute of the Neurological Sciences of Bologna, Bologna, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.|IRCCS Institute of the Neurological Sciences of Bologna, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects; D008297:Male; D009290:Narcolepsy / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D064446:Orexin Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000068797:Orexins / Q000134:cerebrospinal fluid; D014611:Vaccination / Q000009:adverse effects
chemical_list: D000906:Antibodies; C578626:HCRTR2 protein, human; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D064446:Orexin Receptors; D000068797:Orexins; C556153:pandemrix
keywords: HCRTR2; antibodies; autoimmune.; narcolepsy