HLA profiles in immune checkpoint inhibitor-associated neuromuscular adverse events

Background and objectives Immune checkpoint inhibitors (ICIs) can cause neuromuscular adverse events (nmAEs), yet the immunogenetic background of affected patients remains poorly characterized. We descriptively characterized the HLA profile of patients with ICI-associated nmAEs at two tertiary Israeli centers and explored allele and multilocus allele patterns relative to available population references. Methods Eight-locus HLA typing was performed in 17 consecutive patients with ICI-associated nmAEs. Allele and carrier frequencies were descriptively compared with available Israeli and Mediterranean/European population references. Because the study lacked an ancestry-matched ICI-treated control cohort, these comparisons were considered exploratory and hypothesis-generating. Results Six patients had myasthenia gravis (MG), five had myositis, and six had overlap syndromes; median age at onset was 76 years (IQR 72 to 80). HLA-DQA1 05:05 was present in 10/17 patients (58.8%) compared with 19.0% in the reference population ( OR 6.09, 95% CI 2.31 to 16.04, p<0.001, q=0.008 ). DQB1 03:01 was present in 10/17 patients (58.8%). DRB1 11–DQA1 05:05–DQB1 03:01 multilocus allele combination was observed in 9/17 patients (52.9%). HLA-B 35 and C 04:01 co-occurred in 7/17 patients (41.2%). DRB1 11 carrier status was not significantly associated with cardiac involvement (7/9 vs. 4/8, p=0.335) or mortality (4/9 vs. 1/8, p=0.294). Conclusions This small descriptive cohort identified recurrent HLA class II allele patterns among patients with ICI-associated neuromuscular adverse events, most prominently DQA1 05:05 and its frequent co-occurrence with DQB1 03:01 and DRB1*11. These findings are exploratory and cannot distinguish susceptibility to ICI-associated neuromuscular toxicity from a broader predisposition to neuromuscular autoimmunity or population structure. Validation in larger, ancestry-matched cohorts including ICI-treated patients without immune-related adverse events is required.