HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis
(2024) In European Journal of Endocrinology 191(1). p.9-16- 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... (More)
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.
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- author
- Ono, Mayo ; Nagao, Mototsugu LU ; Takeuchi, Haruki ; Fukunaga, Etsuya ; Nagamine, Tomoko ; Inagaki, Kyoko ; Fukuda, Izumi and Iwabu, Masato
- publishing date
- 2024-07-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Diabetes Mellitus, Type 1/genetics, Adrenocorticotropic Hormone/deficiency, Immune Checkpoint Inhibitors/adverse effects, Male, Female, HLA Antigens/genetics, Adrenal Insufficiency/genetics, Adult, Middle Aged, Neoplasms/drug therapy, Endocrine System Diseases, Hypoglycemia, Genetic Diseases, Inborn
- in
- European Journal of Endocrinology
- volume
- 191
- issue
- 1
- pages
- 9 - 16
- publisher
- Society of the European Journal of Endocrinology
- external identifiers
-
- scopus:85197534339
- pmid:38917237
- ISSN
- 1479-683X
- DOI
- 10.1093/ejendo/lvae081
- language
- English
- LU publication?
- no
- additional info
- © The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
- id
- e3a3760b-3bf9-480c-b538-eed7613ad529
- date added to LUP
- 2025-01-12 02:03:52
- date last changed
- 2025-06-29 18:29:15
@article{e3a3760b-3bf9-480c-b538-eed7613ad529,
abstract = {{<p>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.</p><p>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).</p><p>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.</p><p>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.</p>}},
author = {{Ono, Mayo and Nagao, Mototsugu and Takeuchi, Haruki and Fukunaga, Etsuya and Nagamine, Tomoko and Inagaki, Kyoko and Fukuda, Izumi and Iwabu, Masato}},
issn = {{1479-683X}},
keywords = {{Humans; Diabetes Mellitus, Type 1/genetics; Adrenocorticotropic Hormone/deficiency; Immune Checkpoint Inhibitors/adverse effects; Male; Female; HLA Antigens/genetics; Adrenal Insufficiency/genetics; Adult; Middle Aged; Neoplasms/drug therapy; Endocrine System Diseases; Hypoglycemia; Genetic Diseases, Inborn}},
language = {{eng}},
month = {{07}},
number = {{1}},
pages = {{9--16}},
publisher = {{Society of the European Journal of Endocrinology}},
series = {{European Journal of Endocrinology}},
title = {{HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis}},
url = {{http://dx.doi.org/10.1093/ejendo/lvae081}},
doi = {{10.1093/ejendo/lvae081}},
volume = {{191}},
year = {{2024}},
}