Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.

ABSTRACT: 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. Onset is seasonal and associated with influenza A, notably pandemic 2009 H1N1 (pH1N1) infection and vaccination (Pandemrix). Peptides derived from HCRT and influenza A, including pH1N1, were screened for DQ0602 binding and presence of cognate DQ0602 tetramer-peptide-specific CD4⁺ T cells tested in 35 T1N cases and 22 DQ0602 controls. Higher reactivity to influenza pHA_273-287 (pH1N1 specific), PR8 (H1N1 pre-2009 and H2N2)-specific NP_17-31 and C-amidated but not native version of HCRT_54-66 and HCR

SUBMITTER: Luo G 

PROVIDER: S-EPMC6310865 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature