Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain

被引:101
作者
Kornum, Birgitte Rahbek [1 ]
Faraco, Juliette [1 ]
Mignot, Emmanuel [1 ]
机构
[1] Stanford Univ, Sch Med, Stanford Ctr Sleep Sci & Med, Palo Alto, CA 94304 USA
关键词
CENTRAL-NERVOUS-SYSTEM; CLASS-II COMPLEXES; MHC CLASS-I; ENCEPHALITIS LETHARGICA; HLA DQB1-ASTERISK-0602; COMMON VARIANTS; LOCUS-COERULEUS; CATAPLEXY; OREXIN; SLEEP;
D O I
10.1016/j.conb.2011.09.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes narcolepsy with cataplexy. An autoimmune basis for the disease has long been suspected and recent results have greatly strengthened this hypothesis. Narcolepsy with hcrt deficiency is now known to be associated with a Human Leukocyte Antigen (HLA) and T-cell receptor (TCR) polymorphisms, suggesting that an autoimmune process targets a single peptide unique to hcrt-cells via specific HLA-peptide-TCR interactions. Recent data have shown a robust seasonality of disease onset in children and associations with Streptococcus Pyogenes, and influenza A H1N1-infection and H1N1-vaccination, pointing towards processes such as molecular mimicry or bystander activation as crucial for disease development. We speculate that upper airway infections may be common precipitants of a whole host of CNS autoimmune complications including narcolepsy.
引用
收藏
页码:897 / 903
页数:7
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