Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases
| العنوان: | Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases |
|---|---|
| المؤلفون: | Markku Partinen, Emmanuel Mignot, Christopher M. Adams, Fabio Pizza, Mélodie Bonvalet, Ryan D. Leib, Aditya Ambati, Ling Lin, Louis Jacob, Guo Luo, Giuseppe Plazzi |
| المساهمون: | Luo, Guo, Lin, Ling, Jacob, Loui, Bonvalet, Mã©lodie, Ambati, Aditya, Plazzi, Giuseppe, Pizza, Fabio, Leib, Ryan, Adams, Christopher M., Partinen, Markku, Mignot, Emmanuel Jean-Marie |
| المصدر: | PLoS ONE PLoS ONE, Vol 12, Iss 12, p e0187305 (2017) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cataplexy, Physiology, lcsh:Medicine, medicine.disease_cause, Biochemistry, Immunoglobulin G, Mass Spectrometry, 0302 clinical medicine, Spectrum Analysis Techniques, HEK293 Cell, Orexin Receptors, Immune Physiology, Medicine and Health Sciences, Pandemrix, Public and Occupational Health, Enzyme-Linked Immunoassays, lcsh:Science, Child, Staining, education.field_of_study, Vaccines, Multidisciplinary, Immune System Proteins, biology, Cell Staining, Flow Cytometry, Autoantibodie, Vaccination and Immunization, Molecular mimicry, Infectious Diseases, Neurology, Spectrophotometry, Female, Cytophotometry, Antibody, medicine.symptom, Case-Control Studie, Human, Research Article, Infectious Disease Control, Adolescent, Population, Immunology, Enzyme-Linked Immunosorbent Assay, Research and Analysis Methods, Antibodies, 03 medical and health sciences, medicine, Humans, Autoantibodies, Case-Control Studies, HEK293 Cells, Narcolepsy, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), education, Immunoassays, Biochemistry, Genetics and Molecular Biology (all), business.industry, lcsh:R, Autoantibody, Biology and Life Sciences, Proteins, Correction, medicine.disease, Orexin Receptor, Molecular biology, Dyssomnias, 030104 developmental biology, Specimen Preparation and Treatment, biology.protein, Immunologic Techniques, lcsh:Q, Preventive Medicine, business, Sleep Disorders, 030217 neurology & neurosurgery |
| الوصف: | Background A recent publication suggested molecular mimicry of a nucleoprotein (NP) sequence from A/Puerto Rico/8/1934 (PR8) strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT) receptor 2 (anti-HCRTR2) autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera). In this study, we re-examined this hypothesis through mass spectrometry (MS) characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1)-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies. Methods MS characterization of Pandemrix® (2 batches), Arepanrix® (4 batches) and Focetria® (1 batch) was conducted with mapping of NP 116I or 116M spectrogram. Two sets of narcolepsy cases and controls were used: 40 post Pandemrix® narcolepsy (PP-N) cases and 18 age-matched post Pandemrix® controls (PP-C), and 48 recent (≤6 months) early onset narcolepsy (EO-N) cases and 70 age-matched other controls (O-C). Anti-HCRTR2 autoantibodies were detected using three strategies: (1) Human embryonic kidney (HEK) 293T cells with transient expression of HCRTR2 were stained with human sera and then analyzed by flow cytometer; (2) In vitro translation of [35S]-radiolabelled HCRTR2 was incubated with human sera and immune complexes of autoantibody and [35S]-radiolabelled HCRTR2 were quantified using a radioligand-binding assay; (3) Optical density (OD) at 450 nm (OD450) of human serum immunoglobulin G (IgG) binding to HCRTR2 stably expressed in Chinese hamster ovary (CHO)-K1 cell line was measured using an in-cell enzyme-linked immunosorbent assay (ELISA). Results NP 116M mutations were predominantly present in all batches of Pandemrix®, Arepanrix® and Focetria®. The wild-type NP109-123 (ILYDKEEIRRIWRQA), a mimic to HCRTR234-45 (YDDEEFLRYLWR), was not found to bind to DQ0602. Three or four subjects were found positive for anti-HCRTR2 autoantibodies using two strategies or the third one, respectively. None of the post Pandemrix® narcolepsy cases (0 of 40 sera) was found positive with all three strategies. Conclusion Anti-HCRTR2 autoantibody is not a significant biological feature of narcolepsy or of post Pandemrix® autoimmune responses. |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd26df3d44d9006367774b37909255cbTest https://hdl.handle.net/11380/1206108Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cd26df3d44d9006367774b37909255cb |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |