title: Anti-LGI1 encephalitis is associated with unique HLA subtypes.
abstract: OBJECTIVE
  Autoimmune encephalitis (AE), represented by anti-leucine-rich glioma-inactivated 1 (anti-LGI1) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes.
  
  
  METHODS
  We compared the HLA genotypes of 11 anti-LGI1 and 17 anti-NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans.
  
  
  RESULTS
  Anti-LGI1 encephalitis was associated with the DRB1*07:01-DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti-LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti-NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA-peptide binding prediction algorithms and computational docking underpinned the close relationship.
  
  
  CONCLUSIONS
  This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.
authors.forename: Jun-Sang
authors.initials: JS
authors.lastname: Sunwoo
authors.affiliation: Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
authors.forename: Jung-Ick
authors.initials: JI
authors.lastname: Byun
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Shin
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Jun
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Han Sang
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Woo-Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Ah Reaum
authors.initials: AR
authors.lastname: Yang
authors.affiliation: Medical Research Collaborating Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
authors.forename: Kyung-Il
authors.initials: KI
authors.lastname: Park
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.|Protein Metabolism Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology*; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins