Tae-Joon Kim1, Soon-Tae Lee1, Jangsup Moon1, Jun-Sang Sunwoo2, Jung-Ick Byun3, Jung-Ah Lim1, Yong-Won Shin1, Jin-Sun Jun1, Han Sang Lee1, Woo-Jin Lee1, Ah Reaum Yang1, Yunhee Choi4, Kyung-Il Park5, Keun-Hwa Jung1, Ki-Young Jung1, Manho Kim1,6, Sang Kun Lee1, Kon Chu1. 1. Department of Neurology, Seoul National University Hospital, Seoul, South Korea. 2. Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, South Korea. 3. Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea. 4. Medical Research Collaborating Center, Seoul National University Hospital, Seoul, South Korea. 5. Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea. 6. Protein Metabolism Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
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. INTERPRETATION: 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.
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 encephalitispatients to the control groups, which consisted of 210 epilepsypatients and 485 healthy Koreans. RESULTS: Anti-LGI1encephalitis 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-LGI1encephalitis 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. INTERPRETATION: This finding suggests that most anti-LGI1encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.
Authors: Thaís Armangue; Marianna Spatola; Alexandru Vlagea; Simone Mattozzi; Marc Cárceles-Cordon; Eloy Martinez-Heras; Sara Llufriu; Jordi Muchart; María Elena Erro; Laura Abraira; German Moris; Luis Monros-Giménez; Íñigo Corral-Corral; Carmen Montejo; Manuel Toledo; Luis Bataller; Gabriela Secondi; Helena Ariño; Eugenia Martínez-Hernández; Manel Juan; Maria Angeles Marcos; Laia Alsina; Albert Saiz; Myrna R Rosenfeld; Francesc Graus; Josep Dalmau Journal: Lancet Neurol Date: 2018-07-23 Impact factor: 44.182