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Link between HLA alleles and anti-NMDAR encephalitis
  1. Noriko Isobe
  1. Department of Neurological Therapeutics, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  1. Correspondence to Dr Noriko Isobe, Department of Neurological Therapeutics, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; kuroki{at}

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HLA-DRB1*16:02 is a disease susceptibility allele for anti-NMDAR encephalitis in the Chinese Han population

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the major types of antibody-mediated autoimmune encephalitis. It was originally reported to be highly prevalent in young women with ovarian teratoma, but later studies found that the cases were not limited to young women with tumours; it was observed in both genders of any age, irrespective of tumour positivity.1 Clinical manifestations include neuropsychiatric syndrome with movement disorders, seizures and autonomic dysfunction.

Recently, several studies have reported human leucocyte antigen (HLA) associations with antibody-mediated encephalitis, including anti-NMDAR encephalitis and anti-leucine-rich glioma-inactivated1 (LGI1) encephalitis. While HLA-DRB1*07:01 or its extended haplotypes with HLA-DQA1*02:01 or HLA-DQB1*02:02 were strongly associated with anti-LGI1 encephalitis, with extremely high effect sizes in multiple studies conducted in different populations,2 3 HLA associations with anti-NMDAR encephalitis have been less conclusive; only a borderline association with HLA-B*07:02 in German patients with anti-NMDAR encephalitis has been reported.2

In their JNNP paper, Shu et al investigated whether anti-NMDAR encephalitis was associated with any HLA alleles, utilising samples from 61 patients with anti-NMDAR encephalitis and 571 healthy controls from the Chinese Han population.4 In this study, six HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA -DQA1 and HLA -DQB1) were typed using a PCR sequence-based typing method, while the German study mentioned above imputed HLA alleles from single nucleotide polymorphisms (SNPs) genotyped on a genome-wide SNP chip array.2 Shu et al demonstrated that the HLA-DRB1*16:02 allele was associated with disease susceptibility (allele frequency: 14.75% in cases vs 4.82% in controls; OR 3.42 (95% CI 1.82 to 6.17)) and the association did not depend on the positivity of tumours. Furthermore, the patients with anti-NMDAR encephalitis with HLA-DRB1*16:02 tended to respond less efficiently to treatment, suggesting that certain genetic backgrounds may contribute to distinct disease development.

Although replication studies are required in other cohorts from multiple populations to assess whether the findings are commonly shared across populations or are unique to specific populations, this study highlights the possible link between HLA alleles and anti-NMDAR encephalitis and paves the way for further discussions on how and what kinds of T cells contribute to the disease pathogenesis.


We thank Ann Turnley, PhD, from Edanz Group ( for editing a draft of this manuscript.


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  • Contributors Only NI is the author and no additional contributorship exists.

  • Funding This work was supported in part by a research grant from the Japan Intractable Disease Research Foundation and by a Grant-in-Aid for Scientific Research C (18K0752) from the Japan Society for the Promotion of Science, Japan.

  • Competing interests NI has received research support from Mitsubishi Tanabe Pharma, Osoegawa Neurology Clinic, and Japan Blood Products Organization, honoraria from Mitsubishi Tanabe Pharma and Alexion, and is a consultant for Oxford Health Policy Forum CIC.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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