Evidence map›Paper›PMID 29220370›Full record

ArticlePloS one2017

Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

Guo Luo, Ling Lin, Louis Jacob, Mélodie Bonvalet, Aditya Ambati, Giuseppe Plazzi, Fabio Pizza, Ryan Leib, Christopher M Adams, Markku Partinen and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Characterization of T cell receptors reactive to HCRTProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  4. Article
  5. Review
  6. Article
  7. Narcolepsy risk and COVID-19.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2020
    Article
  8. Immunotherapy in Narcolepsy.Current treatment options in neurology · 2020
    Review
  9. Review
  10. No evidence of autoimmunity to human OXJournal of translational autoimmunity · 2020
    Article
  11. Article
  12. Update on narcolepsy.Journal of neurology · 2019
    Review
  13. The neurobiological basis of narcolepsy.Nature reviews. Neuroscience · 2019
    Review
  14. Article
  15. Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Guo LuoStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.ORCID http://orcid.org/0000-0002-0786-8131
Ling LinStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
Louis JacobStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
Mélodie BonvaletStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
Aditya AmbatiStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
Giuseppe PlazziDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Fabio PizzaDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Ryan LeibStanford University Mass Spectrometry, Palo Alto, California, United States of America.
Christopher M AdamsStanford University Mass Spectrometry, Palo Alto, California, United States of America.
Markku PartinenHelsinki Sleep Clinic, Helsinki, Finland.
Emmanuel Jean-Marie MignotStanford University Center for Sleep Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, United States of America.
Stanford University · USInstitute of Neurological Sciences · ITPalo Alto University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA 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.

methodsMS 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).

resultsNP 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.

conclusionAnti-HCRTR2 autoantibody is not a significant biological feature of narcolepsy or of post Pandemrix® autoimmune responses.

Indexed as

AdolescentAutoantibodiesCase-Control StudiesChildEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHEK293 CellsHumansMaleMass SpectrometryNarcolepsyOrexin ReceptorsAutoantibodiesOrexin Receptors

Identifiers

PMID29220370
PMCPMC5722318
OpenAlexW2774359945

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.