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

Author: Mueller, S.H.; Farber, A.; Pruss, H.; Melzer, N.; Golombeck, K.S.; Kumpfel, T.; Thaler, F.; Elisak, M.; Lewerenz, J.; Kaufmann, M.; Suhs, K.-W.; Ringelstein, M.; Kellinghaus, C.; Bien, C.G.; Kraft, A.; Zettl, U.K.; Ehrlich, S.; Handreka, R.; Rostasy, K.; Then Bergh, F.; Faiss, J.H.; Lieb, W.; Franke, A.; Kuhlenbaumer, G.; Wandinger, K.-P.; Leypoldt, F.

Description: 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 x 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 x 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.

Subject headings: Adolescent; Adult; Aged; Autoantibodies/metabolism; Encephalitis/genetics/immunology/metabolism; Female; Genetic Predisposition to Disease/genetics; Genome-Wide Association Study; Hashimoto Disease/genetics/immunology/metabolism; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide/genetics; Protein-Serine-Threonine Kinases/genetics; Proteins/genetics/immunology; Receptors, N-Methyl-D-Aspartate/immunology; Young Adult

Publication year: 2018

Journal or book title: Annals of Neurology

Volume: 83

Issue: 4

Pages: 863-869

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Type: Journal Article

Serial number: 3035