title: Autoantibody targets in vaccine-associated narcolepsy.
abstract: Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Häggmark-Månberg
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Arash
authors.initials: A
authors.lastname: Zandian
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Forsström
authors.affiliation: c Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.affiliation: c Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Izaura
authors.initials: I
authors.lastname: Lima Bomfim
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hellström
authors.affiliation: d Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm , Sweden.
authors.forename: Lisen
authors.initials: L
authors.lastname: Arnheim-Dahlström
authors.affiliation: e Division of Pediatrics , Department of Clinical Sciences, Faculty of Medicine, Lund University , Lund , Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Hallböök
authors.affiliation: e Division of Pediatrics , Department of Clinical Sciences, Faculty of Medicine, Lund University , Lund , Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Darin
authors.affiliation: f Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: g Helsinki Sleep Clinic, Vitalmed Research Centre , Helsinki , Finland , and.|h Department of Clinical Neurosciences , University of Helsinki , Helsinki , Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Partinen
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.affiliation: c Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: a Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.|b KTH Center for Applied Proteomics, SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology , Stockholm , Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D016022:Case-Control Studies; D002648:Child; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000209:etiology*; D014612:Vaccines / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D014612:Vaccines; D015720:5'-Nucleotidase; C552626:NT5C1A protein, human
keywords: Narcolepsy; autoantibody; protein microarray; serum; vaccine-associated