目的:在癌症治疗中广泛使用免疫检查点抑制剂(ICIs)导致报告的免疫治疗相关内分泌疾病病例数增加。这项研究旨在分析和比较两种情况下与ICI诱导的1型糖尿病(ICI-T1D)和孤立的促肾上腺皮质激素缺乏症(ICI-IAD)相关的人类白细胞抗原(HLA)特征。
方法:在22例ICI-T1D无并发IAD患者中检查了HLA特征的发生频率,包括16例来自全国报告的患者(ICI-T1D组)和14例ICI-IAD患者,但不同时发生T1D(ICI-IAD组)。还比较了11例ICI-T1D和ICI-IAD患者的HLA特征,包括8份来自全国范围的报告(ICI-T1D/IAD组)。
结果:在ICI-T1D组中,HLA-DRB1*09:01-DQB1*03:03和DQA1*03:02与DRB1*09:01-DQB1*03:03和DRB1*13:02-DQB1*06:04对ICI-T1D敏感,而DRB1*15:02-DQB1*06:01对ICI-T1D有保护作用。在ICI-IAD组中,DPB1*09:01,C*12:02-B*52:01,DRB1*15:02-DRB1*06:01,强连锁不平衡,与ICI-IAD易感性相关。此外,在ICI-T1D/IAD组中未检测到DRB1*15:02-DRB1*06:01。
结论:本研究揭示了与ICI-T1D和ICI-IAD相关的特异性HLA特征。此外,HLA-DRB1*15:02-DRB1*06:01,ICI-IAD易感HLA单倍型,与ICI-T1D保护性HLA单倍型一致,提示在ICI-IAD患者中,DRB1*15:02-DRB1*06:01的存在可以防止T1D的同时发生.
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*09:01-DQB1*03:03 and DQA1*03:02, which are in linkage disequilibrium with DRB1*09:01-DQB1*03:03 and DRB1*13:02-DQB1*06:04, were susceptible to ICI-T1D, whereas DRB1*15:02-DQB1*06:01 was protective against ICI-T1D. In the ICI-IAD group, DPB1*09:01, C*12:02-B*52:01, and DRB1*15:02-DRB1*06:01, which are in strong linkage disequilibrium, were associated with susceptibility to ICI-IAD. Moreover, DRB1*15:02-DRB1*06:01 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*15:02-DRB1*06:01, an ICI-IAD-susceptible HLA haplotype, coincides with the ICI-T1D-protective HLA haplotype, suggesting that the presence of DRB1*15:02-DRB1*06:01 may protect against the co-occurrence of T1D in patients with ICI-IAD.