PMID- 24353159
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20211203
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 5
IP  - 216
DP  - 2013 Dec 18
TI  - CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 
      influenza A epitope in narcolepsy.
PG  - 216ra176
LID - 10.1126/scitranslmed.3007762 [doi]
AB  - Narcolepsy, a disorder strongly associated with human leukocyte antigen 
      (HLA)-DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime 
      sleepiness, cataplexy, and rapid eye movement sleep abnormalities. It is caused 
      by the loss of ~70,000 posterior hypothalamic neurons that produce the 
      wake-promoting neuropeptide hypocretin (HCRT) (orexin). We identified two 
      DQ0602-binding HCRT epitopes, HCRT56-68 and HCRT87-99, that activated a 
      subpopulation of CD4(+) T cells in narcolepsy patients but not in DQ0602-positive 
      healthy control subjects. Because of the established association of narcolepsy 
      with the 2009 H1N1 influenza A strain (pH1N1), we administered a seasonal 
      influenza vaccine (containing pH1N1) to patients with narcolepsy and found an 
      increased frequency of circulating HCRT56-68- and HCRT87-99-reactive T cells. We 
      also identified a hemagglutinin (HA) pHA1 epitope specific to the 2009 H1N1 
      strain, pHA1275-287, with homology to HCRT56-68 and HCRT87-99. In vitro 
      stimulation of narcolepsy CD4(+) T cells with pH1N1 proteins or pHA1275-287 
      increased the frequency of HCRT56-68- and HCRT87-99-reactive T cells. Our data 
      indicate the presence of CD4(+) T cells that are reactive to HCRT in narcolepsy 
      patients and possible molecular mimicry between HCRT and a similar epitope in 
      influenza pH1N1, pHA1275-287.
FAU - De la Herran-Arita, Alberto K
AU  - De la Herran-Arita AK
AD  - Center for Sleep Sciences and Medicine, Stanford School of Medicine, Palo Alto, 
      CA 94304, USA.
FAU - Kornum, Birgitte Rahbek
AU  - Kornum BR
FAU - Mahlios, Josh
AU  - Mahlios J
FAU - Jiang, Wei
AU  - Jiang W
FAU - Lin, Ling
AU  - Lin L
FAU - Hou, Tieying
AU  - Hou T
FAU - Macaubas, Claudia
AU  - Macaubas C
FAU - Einen, Mali
AU  - Einen M
FAU - Plazzi, Giuseppe
AU  - Plazzi G
FAU - Crowe, Catherine
AU  - Crowe C
FAU - Newell, Evan W
AU  - Newell EW
FAU - Davis, Mark M
AU  - Davis MM
FAU - Mellins, Elizabeth D
AU  - Mellins ED
FAU - Mignot, Emmanuel
AU  - Mignot E
LA  - eng
GR  - P50 NS23724/NS/NINDS NIH HHS/United States
GR  - R21 AI095813/AI/NIAID NIH HHS/United States
GR  - U19AI057229/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (H1N1 virus hemagglutinin)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Hemagglutinin Glycoproteins, Influenza Virus)
RN  - 0 (Influenza Vaccines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 0 (pandemrix)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.2.2.5 (CD38 protein, human)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
CIN - Nat Rev Immunol. 2014 Feb;14(2):66-7. PMID: 24445664
CIN - Sci Transl Med. 2014 Jun 25;6(242):242le3. PMID: 24964988
RIN - De la Herran-Arita AK, Kornum BR, Mahlios J, Jiang W, Lin L, Hou T, Macaubas C, 
      Einen M, Plazzi G, Crowe C, Newell EW, Davis MM, Mellins ED, Mignot E. Sci Transl 
      Med. 2014 Jul 30;6(247):247rt1. PMID: 25080479
MH  - ADP-ribosyl Cyclase 1/immunology
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - *Autoimmunity/genetics
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Case-Control Studies
MH  - Child
MH  - Cross Reactions
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - Female
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - Hemagglutinin Glycoproteins, Influenza Virus/genetics/*immunology
MH  - Humans
MH  - Influenza A Virus, H1N1 Subtype/genetics/*immunology
MH  - Influenza Vaccines/adverse effects/immunology
MH  - Influenza, Human/immunology/virology
MH  - Interferon-gamma/biosynthesis
MH  - Intracellular Signaling Peptides and Proteins/genetics/*immunology
MH  - Lymphocyte Activation
MH  - Male
MH  - Membrane Glycoproteins/immunology
MH  - Middle Aged
MH  - Molecular Mimicry/genetics/immunology
MH  - Molecular Sequence Data
MH  - Narcolepsy/etiology/genetics/*immunology
MH  - Neuropeptides/genetics/*immunology
MH  - Orexins
MH  - Sequence Homology, Amino Acid
MH  - Translational Research, Biomedical
MH  - Twins, Monozygotic
MH  - Young Adult
EDAT- 2013/12/20 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/12/20 06:00
PHST- 2013/12/20 06:00 [entrez]
PHST- 2013/12/20 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 5/216/216ra176 [pii]
AID - 10.1126/scitranslmed.3007762 [doi]
PST - ppublish
SO  - Sci Transl Med. 2013 Dec 18;5(216):216ra176. doi: 10.1126/scitranslmed.3007762.