HLA genotyping and clinical characteristics of early-onset and late-onset anti-LGI1 encephalitis: a single-center cohort study in China.
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OBJECTIVES: To investigate the human leukocyte antigen (HLA) associations and clinical characteristics of anti-Leucine-rich glioma-inactivated 1 (LGI1) encephalitis in a Chinese cohort, focusing on potential differences between early-onset and late-onset patients. METHODS: Eighty patients diagnosed with anti-LGI1 encephalitis at Peking Union Medical College Hospital between the years 2016 and 2024 were included. Patients were stratified into early-onset (<50 years, n=22) and late-onset (≥50 years, n=58) groups for clinical features analysis. High-resolution NGS HLA genotyping was performed and compared with 984 healthy controls. Logistic and linear regressions were used to analyze disease susceptibility, age of onset associations, and prognostic factors. RESULTS: Compared with the late-onset group, the early-onset group more frequently presented with generalized tonic-clonic seizures (GTCS) as the initial symptom (45.5% vs. 10.3%, post-hoc p = 0.001), and a lower frequency of psychiatric symptoms (p = 0.047) and amnesia (p = 0.002) during the disease course, presenting with lower mRS scores at onset (p = 0.020). Genetically, DRB1*07:01 was confirmed as the primary risk allele (OR = 10.4, 95% CI 6.01-18.02, pc = 6.78×10-15). DRB1*09:01(OR = 3.67, 95% CI 2.17-6.20, pc = 1.16×10-5) and DQB1*03:03 (OR = 3.25, 95% CI 1.98-5.33, pc = 1.32×10-5) were identified as novel secondary risk alleles in this Chinese cohort. Importantly, specific HLA genotypes were significantly associated with the age of onset. A*02:01 was linked to an earlier onset (β = -9.26; pc = 0.019) and served as a risk factor for the early-onset group, while DRB1*07:01 was associated with a later onset (β = 13.44, pc = 0.006). Diagnostic delay (OR = 1.01, 95% CI 1.00-1.02, p = 0.037) and GTCS (OR = 5.01, 95% CI 1.11-22.66, p = 0.036) were independent predictors of poor prognosis. CONCLUSIONS: This study suggests that early-onset and late-onset anti-LGI1 encephalitis may possess differential immunogenetic and clinical profiles. In addition to the broad susceptibility conferred by DRB1*07:01, the presence of A*02:01 is significantly associated with an earlier onset age. These findings provide insights into the role of HLA genotyping in accounting for the observed differences between early-onset and late-onset patients.