HLA class II alleleDRB1*16:02is associated with anti-NMDAR encephalitis

Abstract

Background and objectiveAetiology and pathogenesis of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the most common autoimmune encephalitis, is largely unknown. Since an association of the disease with the human leucocyte antigen (HLA) has not been shown so far, we here investigated whether anti-NMDAR encephalitis is associated with the HLA locus.MethodsHLA loci of 61 patients with anti-NMDAR encephalitis and 571 healthy controls from the Chinese Han population were genotyped and analysed for this study.ResultsOur results show that the DRB1*16:02 allele is associated with anti-NMDAR encephalitis (OR 3.416, 95% CI 1.817 to 6.174, p=8.9×10−5, padj=0.021), with a higher allele frequency in patients (14.75%) than in controls (4.82%). This association was found to be independent of tumour formation. Besides disease susceptibility, DRB1*16:02 is also related to the clinical outcome of patients during treatment, where patients with DRB1*16:02 showed a lower therapeutic response to the treatment than patients with other HLA alleles (p=0.033). Bioinformatic analysis using HLA peptide-binding prediction algorithms and computational docking suggested a close relationship between the NR1 subunit of NMDAR and the DRB1*16:02.ConclusionsThis study for the first time demonstrates an association between specific HLA class II alleles and anti-NMDAR encephalitis, providing novel insights into the pathomechanism of the disease.

Associations between HLA and autoimmune neurological diseases with autoantibodies

“…No strong HLA association has been reported with anti-NMDAR encephalitis thus far [84,95]. DRB1*16:02 was found to be more frequent in patients than in controls, but it accounted for less than 15% of the alleles of a series of 61 patients (vs. less than 5% in control group; p < 0.05, OR = 3.41, 95% CI [1.81-6.17]) [96]. Moreover, carrier frequencies between paraneoplastic (mostly ovarian teratomas) and non-paraneoplastic cases were similar.…”

“…Moreover, carrier frequencies between paraneoplastic (mostly ovarian teratomas) and non-paraneoplastic cases were similar. The only observed clinical difference was a possible worse response to treatment in DRB1*16:02 carriers [96]. Finally, in a genome-wide association study, a weak association with B*07:02 was described in adult patients with anti-NMDAR encephalitis (21% of the alleles of a sample of n = 49; p < 0.05, OR = 2.32, 95% CI [1.34-4.00]) [95].…”

Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

“…The phenomenons are not rare that one autoimmune disease increases the chance of an additional autoimmune disease, and that autoimmune disease patient has multiple positive antibodies. Recent studies have shown that anti-NMDAR encephalitis was associated with the HLA alleles (23,24). Perhaps, genetic predisposition is the important reason for the increased prevalence of systemic autoantibodies in patients with anti-NMDAR encephalitis.…”

Link between HLA alleles and anti-NMDAR encephalitis

“…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.…”