Clinical Characteristics and Human Leukocyte Antigens in patients with Immune Checkpoint Inhibitor-induced Type 1 Diabetes and Pituitary Dysfunction: A single center prospective study

Abstract

Purpose Immune checkpoint inhibitor (ICI)-induced type 1 diabetes and pituitary dysfunction are life-threatening adverse events, yet there is little clinical data available. We aimed to investigate the clinical characteristics of patients with these adverse events and report their human leukocyte antigen (HLA) profile to determine its relevance. Methods This is a single-center prospective study. We collected clinical and biochemical data and extracted DNA from blood samples. HLA typing was performed using next-generation sequencing. We compared our results with those previously reported in healthy controls and investigated the correlation between HLA and the occurrence of ICI-induced type 1 diabetes and pituitary dysfunction. Results We identified 914 patients treated with ICI in our facility from 1st September, 2017 to 30th June, 2022. Six of these patients developed type 1 diabetes and 14 developed pituitary dysfunction. The duration from the initiation of ICI treatment to the onset of type 1 diabetes or pituitary dysfunction averaged 492 ± 196 days and 191 ± 169 days, respectively. Among the six patients with type 1 diabetes, two were positive for anti-GAD antibody. The frequencies of HLA-DR11, -Cw10, -B61, -DRB1*11:01, and -C*03:04 were significantly higher in patients with ICI-induced type 1 diabetes than in controls. The frequencies of HLA-DR15 and -DRB*15:02 were significantly higher in patients with ICI-induced pituitary dysfunction than in controls. Conclusion This study revealed the clinical characteristics of type 1 diabetes and pituitary dysfunction induced by ICI and the association between specific HLAs and these adverse events.