Screening for autoantibody targets in post‐vaccination narcolepsy using proteome arrays

Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin‐producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®‐vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood...

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Vydáno v:Scandinavian journal of immunology Ročník 91; číslo 4; s. e12864 - n/a
Hlavní autoři: Lind, Alexander, Eriksson, Daniel, Akel, Omar, Ramelius, Anita, Palm, Lars, Lernmark, Åke, Kämpe, Olle, Elding Larsson, Helena, Landegren, Nils
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Wiley Subscription Services, Inc 01.04.2020
Témata:
antigens
antigens/peptides/epitopes
Autoantibodies
Autoantibodies - blood
Autoantigens
Autoantigens - analysis
Autoantigens - immunology
Autoimmune diseases
autoimmunity
Basic Medicine
Diabetes mellitus (insulin dependent)
Dopamine D2 receptors
epitopes
Female
Histocompatibility antigen HLA
Humans
Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
Immunology in the Medical Area (including Cell and Immunotherapy)
Influenza
Influenza Vaccines - adverse effects
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Multiple sclerosis
Narcolepsy
Narcolepsy - immunology
Neurotrophin 1
Orexins
Pandemics
Pathogenesis
peptides
Proopiomelanocortin
Prostaglandin D2
Protein Array Analysis - methods
Protein arrays
Proteins
Proteomes
Sleep
Sleep disorders
Vaccination
autoimmunity
antigens/peptides/epitopes
autoantibodies
ISSN:0300-9475, 1365-3083, 1365-3083
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Shrnutí:Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin‐producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®‐vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two‐step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®‐vaccination. Using arrays of more than 9000 full‐length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first‐degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α‐MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®‐induced NT1.
Bibliografie:Funding information
The study was supported by Alfred Österlunds Stiftelse, Anna och Edwin Bergers Stiftelse, Magnus Bergvalls Stiftelse, Crafoord Foundation, Filip Lundbergs Stiftelse, Fredrik och Ingrid Thurings Stiftelse, the Royal Physiographic Society of Lund‐Hedda and John Forssmans foundation, Gunvor och Josef Anérs Stiftelse, Jerringfonden, Kronprinsessan Lovisas Förening För Barnasjukvård/Stiftelsen Axel Tielmans Minnesfond, Linnéa och Josef Carlssons Stiftelse, Neuro Sweden, Rune Ljungdahls Stiftelse, Stiftelsen Samariten, Stiftelsen till minne av Personalföreningarna i Holmia Försäkring AB, The Gun and Bertil Stohne's Foundation, the Segerfalk Foundation, Svenska Läkaresällskapet, Region Skane FoU, ALF grants, The Swedish Society for Medical Research, The Swedish Association of Endocrinologists, the Swedish Research Council, Strategic Research Area Exodiab Dnr 2009‐1039 and the Swedish Foundation for Strategic Research Dnr IRC15‐0067.
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SourceType-Scholarly Journals-1
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ISSN:0300-9475
1365-3083
1365-3083
DOI:10.1111/sji.12864