Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-03-01
|
| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418300483 |
| _version_ | 1818318623456886784 |
|---|---|
| author | Helle Sadam Arno Pihlak Anri Kivil Susan Pihelgas Mariliis Jaago Priit Adler Jaak Vilo Olli Vapalahti Toomas Neuman Dan Lindholm Markku Partinen Antti Vaheri Kaia Palm |
| author_facet | Helle Sadam Arno Pihlak Anri Kivil Susan Pihelgas Mariliis Jaago Priit Adler Jaak Vilo Olli Vapalahti Toomas Neuman Dan Lindholm Markku Partinen Antti Vaheri Kaia Palm |
| author_sort | Helle Sadam |
| collection | DOAJ |
| description | 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. Keywords: Narcolepsy type 1, H1N1, Pandemrix, Antibody, Prostaglandin, DP1 |
| first_indexed | 2024-12-13T09:56:10Z |
| format | Article |
| id | doaj.art-1f9a1fb9f29247c99e2b7313e57026ba |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T09:56:10Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-1f9a1fb9f29247c99e2b7313e57026ba2022-12-21T23:51:47ZengElsevierEBioMedicine2352-39642018-03-01294759Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody ProfilingHelle Sadam0Arno Pihlak1Anri Kivil2Susan Pihelgas3Mariliis Jaago4Priit Adler5Jaak Vilo6Olli Vapalahti7Toomas Neuman8Dan Lindholm9Markku Partinen10Antti Vaheri11Kaia Palm12Protobios Llc, Mäealuse 4, 12618 Tallinn, Estonia; Department of Gene Technology, Tallinn University of Technology, Akadeemia Tee 15, 12618 Tallinn, EstoniaProtobios Llc, Mäealuse 4, 12618 Tallinn, Estonia; Department of Gene Technology, Tallinn University of Technology, Akadeemia Tee 15, 12618 Tallinn, EstoniaProtobios Llc, Mäealuse 4, 12618 Tallinn, EstoniaProtobios Llc, Mäealuse 4, 12618 Tallinn, EstoniaProtobios Llc, Mäealuse 4, 12618 Tallinn, EstoniaInstitute of Computer Science, University of Tartu, Liivi 2-314, 50409 Tartu, Estonia; Quretec LLC, Ülikooli 6a, 51003 Tartu, EstoniaInstitute of Computer Science, University of Tartu, Liivi 2-314, 50409 Tartu, Estonia; Quretec LLC, Ülikooli 6a, 51003 Tartu, EstoniaDepartment of Virology, Medicum, Haartmaninkatu 3, 00014 University of Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöbergin Katu 2, 00014 University of Helsinki, Finland; Virology and Immunology, HUSLAB, Helsinki University Hospital, 00290 Helsinki, FinlandProtobios Llc, Mäealuse 4, 12618 Tallinn, Estonia; IPDx Immunoprofiling Diagnostics GmbH, Deutscher Platz 5e, 04103 Leipzig, GermanyDepartment of Biochemistry and Developmental Biology, Medicum, Haartmaninkatu 8, 00014 University of Helsinki, Finland; Minerva Foundation Medical Research Institute, Tukholmankatu 8, 00290 Helsinki, FinlandFinnish Narcolepsy Research Center, Helsinki Sleep Clinic, Vitalmed Research Center, Valimotie 21, 00380, Helsinki, FinlandDepartment of Virology, Medicum, Haartmaninkatu 3, 00014 University of Helsinki, FinlandProtobios Llc, Mäealuse 4, 12618 Tallinn, Estonia; Department of Gene Technology, Tallinn University of Technology, Akadeemia Tee 15, 12618 Tallinn, Estonia; Corresponding author at: Protobios Llc, Mäealuse 4, 12618 Tallinn, Estonia.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. Keywords: Narcolepsy type 1, H1N1, Pandemrix, Antibody, Prostaglandin, DP1http://www.sciencedirect.com/science/article/pii/S2352396418300483 |
| spellingShingle | Helle Sadam Arno Pihlak Anri Kivil Susan Pihelgas Mariliis Jaago Priit Adler Jaak Vilo Olli Vapalahti Toomas Neuman Dan Lindholm Markku Partinen Antti Vaheri Kaia Palm Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling EBioMedicine |
| title | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
| title_full | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
| title_fullStr | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
| title_full_unstemmed | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
| title_short | Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling |
| title_sort | prostaglandin d2 receptor dp1 antibodies predict vaccine induced and spontaneous narcolepsy type 1 large scale study of antibody profiling |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418300483 |
| work_keys_str_mv | AT hellesadam prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT arnopihlak prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT anrikivil prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT susanpihelgas prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT mariliisjaago prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT priitadler prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT jaakvilo prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT ollivapalahti prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT toomasneuman prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT danlindholm prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT markkupartinen prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT anttivaheri prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling AT kaiapalm prostaglandind2receptordp1antibodiespredictvaccineinducedandspontaneousnarcolepsytype1largescalestudyofantibodyprofiling |