HLA profiles in immune checkpoint inhibitor-associated neuromuscular adverse events
Abstract
Background and objectivesImmune 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.MethodsEight-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.ResultsSix 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-DQA105:05 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). DQB103:01 was present in 10/17 patients (58.8%). DRB111–DQA105:05–DQB103:01 multilocus allele combination was observed in 9/17 patients (52.9%). HLA-B35 and C04:01 co-occurred in 7/17 patients (41.2%). DRB111 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).ConclusionsThis small descriptive cohort identified recurrent HLA class II allele patterns among patients with ICI-associated neuromuscular adverse events, most prominently DQA105:05 and its frequent co-occurrence with DQB103:01 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.
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BibTeX
@article{rozenberg2026profiles,
title = {{HLA profiles in immune checkpoint inhibitor-associated neuromuscular adverse events}},
author = {Ayal Rozenberg and Esther Ganelin-Cohen and Lilach Gutter Kapon and Shany Guly Gofrit and Alexandra Amiel and Gal Tsur and Adva Levy-Barda and Almog Kaplan and Shlomit Yust Katz and Shahar Shelly},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1926213},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1926213},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - HLA profiles in immune checkpoint inhibitor-associated neuromuscular adverse events
AU - Ayal Rozenberg
AU - Esther Ganelin-Cohen
AU - Lilach Gutter Kapon
AU - Shany Guly Gofrit
AU - Alexandra Amiel
AU - Gal Tsur
AU - Adva Levy-Barda
AU - Almog Kaplan
AU - Shlomit Yust Katz
AU - Shahar Shelly
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1926213
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1926213
AB - Background and objectivesImmune 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.MethodsEight-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.ResultsSix 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-DQA105:05 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). DQB103:01 was present in 10/17 patients (58.8%). DRB111–DQA105:05–DQB103:01 multilocus allele combination was observed in 9/17 patients (52.9%). HLA-B35 and C04:01 co-occurred in 7/17 patients (41.2%). DRB111 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).ConclusionsThis small descriptive cohort identified recurrent HLA class II allele patterns among patients with ICI-associated neuromuscular adverse events, most prominently DQA105:05 and its frequent co-occurrence with DQB103:01 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.
SN - 1664-3224
ER -