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Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study

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Abstract

Purpose

Immune checkpoint inhibitor (ICI) induced type 1 diabetes (T1D) 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 enrolled patients with cancers who were administered ICI and diagnosed as ICI induced T1D (ICI-T1D) and pituitary dysfunction (ICI-PD). Clinical data and extracted DNA from blood samples were collected. 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-T1D and ICI-PD.

Results

We identified 914 patients treated with ICI in our facility from 1st September, 2017 to 30th June, 2022. Six of these patients developed T1D and 15 developed pituitary dysfunction. The duration from the initiation of ICI treatment to the onset of T1D or pituitary dysfunction averaged 492 ± 196 days and 191 ± 169 days. Among the six patients with T1D, 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-T1D than in controls. The frequencies of HLA-DR15 and -DRB*15:02 were significantly higher in patients with ICI-PD than in controls.

Conclusion

This study revealed the clinical characteristics of ICI-T1D and ICI-PD and the association between specific HLAs and these adverse events.

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Acknowledgements

We thank Ms. Yoshiko Togawa (Tokyo Medical University) for her technical assistance.

Author contributions

The study was designed by H. S. and F. Y.. Data analysis was performed by N. H., who also wrote the manuscript. H. S., K. I., H. I., H. A., H. S., J. S., T. M., and R. S. contributed to the discussion and reviewed and edited the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by JSPS KAKENHI (Grant number JP22K07430) and Manda Memorial Foundation.

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Authors and Affiliations

  1. Department of Diabetes, Metabolism, and Endocrinology, Tokyo Medical University, Tokyo, 160-0023, Japan

    Natsuko Hara, Hirotsugu Suwanai, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa & Ryo Suzuki

  2. Department of Diabetes, Endocrinology and Metabolism, Tokyo Medical University Hachioji Medical Center, Tokyo, 193-0998, Japan

    Fumiyoshi Yakou

Authors
  1. Natsuko Hara
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  2. Hirotsugu Suwanai
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  3. Fumiyoshi Yakou
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  5. Hajime Iwasaki
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Corresponding author

Correspondence to Hirotsugu Suwanai.

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Conflict of interest

Financial interests: H.Suwanai receives personal fees from Nippon Boehringer Ingelheim Co., Ltd. R.S. receives personal fees from Ono Pharmaceutical CO., Ltd, and MSD K.K. N.H., F.Y., K.I., H.I., H.A., H.Sakai., J.S. and T.M. have no financial interests to disclose. All authors have no relevant no non-financial interests to disclose.

Ethical approval

The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional review board of Tokyo Medical University (Approval No. T2021-0005). The design of this prospective study is in accordance with STROBE guidelines.

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Written informed consents were obtained from all individual patients included in the study.

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Hara, N., Suwanai, H., Yakou, F. et al. Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study. Endocrine 81, 477–483 (2023). https://doi.org/10.1007/s12020-023-03394-8

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  • DOI: https://doi.org/10.1007/s12020-023-03394-8

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