Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis

Ann Neurol. 2018 Apr;83(4):863-869. doi: 10.1002/ana.25216.

Abstract

We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p = 1.22 × 10-17 , OR = 13.66 [7.50-24.87]). Potential associations, below genome-wide significance, were found with rs72961463 close to the doublecortin-like kinase 2 gene (DCLK2) and rs62110161 in a cluster of zinc-finger genes. HLA allele imputation identified association of anti-LGI1 encephalitis with HLA-II haplotypes encompassing DRB1*07:01, DQA1*02:01 and DQB1*02:02 (p < 2.2 × 10-16 ) and anti-NMDAR encephalitis with HLA-I allele B*07:02 (p = 0.039). No shared genetic risk factors between encephalitides were identified. Ann Neurol 2018;83:863-869.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / metabolism*
  • Encephalitis / genetics*
  • Encephalitis / immunology
  • Encephalitis / metabolism
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / immunology
  • Hashimoto Disease / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Protein-Serine-Threonine Kinases / genetics*
  • Proteins / genetics*
  • Proteins / immunology
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Young Adult

Substances

  • Autoantibodies
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Proteins
  • Receptors, N-Methyl-D-Aspartate
  • DCLK2 protein, human
  • Protein-Serine-Threonine Kinases

Supplementary concepts

  • Hashimoto's encephalitis