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


Stefanie Mueller, Anna Farber, Harald Pruss, Nico Melzer, Kristin Golombeck, Tania Kumpfel, Franziska Thaler, Martin Elisak, Jan Lewerenz, Max Kaufmann, Kurt-Wolfram Suhs, Marius Ringelstein, Christoph Kellinghaus, Christian Bien, Andrea Kraft, Uwe Zettl, Sven Ehrlich, Robert Handreka, Kevin Rostasy, Florian Then Bergh, Jurgen Faiss, Wolfgang Lieb, Andre Franke, Gregor Kuhlenbaumer, Klaus-Peter Wandinger, Frank Leypoldt




Annals of neurology




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. Ann Neurol 2018;83:863-869.