Publications by authors named "Emmanuel Jean-Marie Mignot"
Characterization of T cell receptors reactive to HCRT, pHA, and NP in control and narcolepsy patients.
Proc Natl Acad Sci U S A
August 2022
Narcolepsy type 1 (NT1), a disorder caused by hypocretin/orexin (HCRT) cell loss, is associated with human leukocyte antigen (HLA)-DQ0602 (98%) and T cell receptor (TCR) polymorphisms. Increased CD4 T cell reactivity to HCRT, especially DQ0602-presented amidated C-terminal HCRT (HCRT), has been reported, and homology with pHA flu antigens from pandemic 2009 H1N1, an established trigger of the disease, suggests molecular mimicry. In this work, we extended DQ0602 tetramer and dextramer data to 77 cases and 44 controls, replicating our prior finding and testing 709 TCRs in Jurkat 76 T cells for functional activation.
View Article and Find Full Text PDFType 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA1*01:02/DQB1*06:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected following the 2009 H1N1 pandemic and linked to Pandemrix vaccination, strongly supporting that narcolepsy is an autoimmune disorder. Although recent results suggest CD4+ T cell reactivity to neuropeptide hypocretin/orexin and cross-reactive flu peptide is involved, identification of other autoantigens has remained elusive.
View Article and Find Full Text PDFArticle Synopsis
- - Kleine-Levin syndrome (KLS) is a rare disorder causing severe episodes of sleepiness, cognitive issues, and changes in behavior, with unclear causes linked to brain activity and difficult births.
- - A global study identified a significant genetic association (rs71947865) related to KLS, particularly prevalent in patients with difficult birth histories and previously connected to bipolar disorder and schizophrenia.
- - Despite variations in findings across different sample sizes, the research highlights potential genetic and environmental factors, specifically involving circadian rhythms, that may contribute to the risk of developing KLS.
Article Synopsis
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Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.
Proc Natl Acad Sci U S A
December 2018
Type 1 narcolepsy (T1N) is caused by hypocretin/orexin (HCRT) neuronal loss. Association with the HLA DQB1*06:02/DQA1*01:02 (98% vs. 25%) heterodimer (DQ0602), T cell receptors (TCR) and other immune loci suggest autoimmunity but autoantigens are unknown.
View Article and Find Full Text PDFBackground: 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.