HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis.

ABSTRACT

OBJECTIVE: Widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in the number of reported cases of immunotherapy-related endocrinopathies. This study aimed to analyze and compare human leukocyte antigen (HLA) signatures associated with ICI-induced type 1 diabetes (ICI-T1D) and isolated adrenocorticotropic hormone deficiency (ICI-IAD) in patients with both conditions. METHODS: HLA signatures were examined for their frequencies of occurrence in 22 patients with ICI-T1D without concurrent IAD, including 16 patients from nationwide reports (ICI-T1D group) and 14 patients with ICI-IAD without concurrent T1D (ICI-IAD group). The HLA signatures were also compared for their respective frequencies in 11 patients with ICI-T1D and ICI-IAD, including eight from nationwide reports (ICI-T1D/IAD group). RESULTS: In the ICI-T1D group, HLA-DRB1*0901-DQB1*0303 and DQA1*0302, which are in linkage disequilibrium with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0604, were susceptible to ICI-T1D, whereas DRB1*1502-DQB1*0601 was protective against ICI-T1D. In the ICI-IAD group, DPB1*0901, C*1202-B*5201, and DRB1*1502-DRB1*0601, which are in strong linkage disequilibrium, were associated with susceptibility to ICI-IAD. Moreover, DRB1*1502-DRB1*0601 was not detected in the ICI-T1D/IAD group. CONCLUSIONS: This study revealed specific HLA signatures associated with ICI-T1D and ICI-IAD. Moreover, HLA-DRB1*1502-DRB1*0601, an ICI-IAD-susceptible HLA haplotype, coincides with the ICI-T1D-protective HLA haplotype, suggesting that the presence of DRB1*1502-DRB1*0601 may protect against the co-occurrence of T1D in patients with ICI-IAD.