HLA-DRB1*03:01 is associated with female sex and younger age of anti-LGI1 encephalitis.

BACKGROUND AND PURPOSE

This study was undertaken to investigate the association between human leukocyte antigen (HLA) genotype and clinical characteristics of anti-LGI1 encephalitis.

METHODS

HLA genotyping was performed in 34 patients with anti-LGI1 encephalitis admitted to West China Hospital between April 2014 and May 2021, as well as in 305 healthy controls. The online tool NetMHCIIpan 4.0 and AutoDock Vina software were used to predict binding between LGI1 peptide and HLA class II molecules.

RESULTS

Risk of anti-LGI1 encephalitis was strongly associated with the DRB103:01 allele (odds ratio [OR] = 4.31, 95% confidence interval [CI] = 1.96-9.25, corrected p = 2.75 × 10 ) and the DRB103:01-DQB102:01 haplotype (OR = 4.45, 95% CI = 2.02-9.59, corrected p = 2.94 × 10 ). Compared to carriers of the DRB107:01 allele, those with the DRB103:01 allele were more likely to be female (93.3% vs. 33.3%, p = 0.004) and to be younger (median age = 38 vs. 65 years, p < 0.001). DRB103:01 carriers showed stronger response to immunotherapy than carriers of the DRB107:01 allele, based on median score decrease on the modified Rankin scale (2, interquartile range = 1-2 vs. 1, interquartile range = 0-1; p = 0.03) at 4 weeks after immunotherapy. Prediction and docking algorithms suggested that the LGI1 peptide can bind to the DRB103:01 molecule strongly.

CONCLUSIONS

The strong association between anti-LGI1 encephalitis and certain HLA class II alleles supports a primary autoimmune origin for the disease. Carriers of the DRB1*03:01 allele in Chinese patients with anti-LGI1 encephalitis are more likely to be female, to suffer earlier disease onset, and to respond better to immunotherapy.