Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1 : Large-scale Study of Antibody Profiling

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Sadam , H , Pihlak , A , Kivil , A , Pihelgas , S , Jaago , M , Adler , P , Vilo , J , Vapalahti , O , Neuman , T , Lindholm , D , Partinen , M , Vaheri , A & Palm , K 2018 , ' Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1 : Large-scale Study of Antibody Profiling ' , EBioMedicine , vol. 29 , pp. 47-59 . https://doi.org/10.1016/j.ebiom.2018.01.043

Title: Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1 : Large-scale Study of Antibody Profiling
Author: Sadam, Helle; Pihlak, Arno; Kivil, Anri; Pihelgas, Susan; Jaago, Mariliis; Adler, Priit; Vilo, Jaak; Vapalahti, Olli; Neuman, Toomas; Lindholm, Dan; Partinen, Markku; Vaheri, Antti; Palm, Kaia
Contributor organization: HUSLAB
Veterinary Microbiology and Epidemiology
Veterinary Biosciences
Olli Pekka Vapalahti / Principal Investigator
Viral Zoonosis Research Unit
Department of Virology
Medicum
Clinicum
University of Helsinki
Department of Biochemistry and Developmental Biology
HUS Neurocenter
Date: 2018-03
Language: eng
Number of pages: 13
Belongs to series: EBioMedicine
ISSN: 2352-3964
DOI: https://doi.org/10.1016/j.ebiom.2018.01.043
URI: http://hdl.handle.net/10138/234394
Abstract: AbstractBackground Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. Methods Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA). Samples from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16 Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals. The diagnosis of NT1 was defined by the American Academy of Sleep Medicine international criteria of sleep disorders v3. Findings Our data showed that although the immunoprofiles toward vaccination were generally similar in study groups, there were also striking differences in immunoprofiles between sNT1 and Pdmx-NT1 groups as compared with controls. Prominent immune response was observed to a peptide epitope derived from prostaglandin D2 receptor (DP1), as well as peptides homologous to B cell lymphoma 6 protein. Further validation confirmed that these can act as true antigenic targets in discriminating NT1 diseased along with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1. Interpretation We propose that DP1 is a novel molecular target of autoimmune response and presents a potential diagnostic biomarker for NT1. DP1 is involved in the regulation of non-rapid eye movement (NREM) sleep and thus alterations in its functions could contribute to the disturbed sleep regulation in NT1 that warrants further studies. Together our results also show that MVA is a helpful method for finding novel peptide antigens to classify human autoimmune diseases, possibly facilitating the design of better therapies.
Subject: Narcolepsy type 1
H1N1
Pandemrix
Antibody
Prostaglandin
DP1
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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