HLA typing in anti-GAD antibody associated epilepsy

Objective: Anti-GAD65 antibodies have been identified in people with epilepsy for many years, but their pathophysiological relevance is still debated. Susceptibility to autoimmune disease has been associated with Human Leukocyte Antigen (HLA) subtypes. Therefore, this study aimed to determine if there are common HLA types in anti-GAD65 antibody associated epilepsy cases compared to epilepsy controls.

Methods: People with anti-GAD65 associated epilepsy and epilepsy controls were recruited from three Brisbane Hospitals from 2021 to 2023. Cases had high titre anti-GAD65 antibodies confirmed in CSF. High resolution genotyping for class I and II HLA to 3 fields was performed using next generation sequencing.

Results: 10 anti-GAD65 cases (8 with epilepsy and 2 with post-encephalitic epilepsy) and 45 controls were included. 6 cases (all female) had co-morbid autoimmune disease. A single class II association was found for DPB1*02 (Padj = 0.0109), which was identified in 7 of the cases (70 % vs 7.7 % controls). Significant association was preserved at high resolution for HLA-DPB1*02:02:01.

Conclusion: HLA association in anti-GAD65 antibody associated epilepsy might provide preliminary evidence to implicate an immune aetiology. DPB1*02 may confer a susceptibility to anti-GAD65 associated epilepsy and this class II association suggests a role for T cells in the pathophysiology.