Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling
| العنوان: | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
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| المؤلفون: | Toomas Neuman, Anri Kivil, Priit Adler, Dan Lindholm, Helle Sadam, Olli Vapalahti, Susan Pihelgas, Antti Vaheri, Markku Partinen, Jaak Vilo, Mariliis Jaago, Kaia Palm, Arno Pihlak |
| المساهمون: | 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 |
| المصدر: | EBioMedicine EBioMedicine, Vol 29, Iss, Pp 47-59 (2018) DOAJ-Articles HELDA-Digital Repository of the University of Helsinki Sygma European Union Open Data Portal PubMed Central UnpayWall ORCID Microsoft Academic Graph |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Narcolepsy type 1, Prostaglandin, Receptors, Prostaglandin, lcsh:Medicine, Autoimmunity, Antibodies, Viral, Autoantigens, Epitope, Epitopes, Influenza A Virus, H1N1 Subtype, 0302 clinical medicine, Pandemrix, DP1, Child, Antigens, Viral, Neurons, Vaccines, lcsh:R5-920, biology, Mimotope, H1N1, General Medicine, Prognosis, 3. Good health, Influenza Vaccines, Female, Antibody, lcsh:Medicine (General), Research Paper, Adult, Adolescent, Non-rapid eye movement sleep, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Immune system, Antigen, Influenza, Human, medicine, Humans, Amino Acid Sequence, Autoantibodies, Narcolepsy, business.industry, lcsh:R, medicine.disease, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, Peptides, business, Biomarkers, Epitope Mapping, 030217 neurology & neurosurgery |
| الوصف: | Highlights • Using large-scale antibody profiling, differences between narcolepsy type 1 (NT1) and healthy controls became evident. • Prostaglandin D2 receptor DP1 was delineated as a novel autoantigenic target in NT1. • Utility of a 3-biomarker ELISPOT assay to assess exposure to H1N1 influenza virus and susceptibility to NT1 was demonstrated. This study reports on the diagnostic value of novel clinical biomarkers for detecting spontaneous and Pandemrix vaccine-associated NT1 and for stratification of A/H1N1 flu-specific response. Large-scale antibody profiling approach revealed the broad scope and high heterogeneity of NT1-associated immune response. We found a strong autoimmune-like response to prostaglandin D2 receptor DP1 suggesting a firm link between DP1/PDG2 and histamine pathways and the molecular basis of NT1. Together our results warrant further investigation of autoimmune ("self-") response in particular to PDG2 biosynthesis pathway as antibodies to the latter may modify the function of pharmaceutical compounds aimed at treating NT1. Background 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. |
| اللغة: | English |
| تدمد: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2018.01.043 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a7da6cca15cea45976da0126be4f999 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0a7da6cca15cea45976da0126be4f999 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2018.01.043 |