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

Mayo Ono; Mototsugu Nagao; Haruki Takeuchi; Etsuya Fukunaga; Tomoko Nagamine; Kyoko Inagaki; Izumi Fukuda; Masato Iwabu

doi:10.1093/ejendo/lvae081

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

Mayo Ono, Mototsugu Nagao, Haruki Takeuchi, Etsuya Fukunaga, Tomoko Nagamine, Kyoko Inagaki, Izumi Fukuda, Masato Iwabu

Nippon Medical School

Research output: Contribution to journal › Article › peer-review

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*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.

Original language	English
Pages (from-to)	9-16
Journal	European Journal of Endocrinology
Volume	191
Issue number	1
DOIs	https://doi.org/10.1093/ejendo/lvae081
Publication status	Published - 2024 Jul 2
Externally published	Yes

Bibliographical note

© 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 [email protected] 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 [email protected].

Subject classification (UKÄ)

Endocrinology and Diabetes

Free 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/ejendo/lvae081

Cite this

@article{e3a3760b3bf9480cb538eed7613ad529,

title = "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*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.",

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",

author = "Mayo Ono and Mototsugu Nagao and Haruki Takeuchi and Etsuya Fukunaga and Tomoko Nagamine and Kyoko Inagaki and Izumi Fukuda and Masato Iwabu",

note = "{\textcopyright} 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 [email protected] 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 [email protected].",

year = "2024",

month = jul,

day = "2",

doi = "10.1093/ejendo/lvae081",

language = "English",

volume = "191",

pages = "9--16",

journal = "European Journal of Endocrinology",

issn = "1479-683X",

publisher = "Society of the European Journal of Endocrinology",

number = "1",

}

TY - JOUR

T1 - HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis

AU - Ono, Mayo

AU - Nagao, Mototsugu

AU - Takeuchi, Haruki

AU - Fukunaga, Etsuya

AU - Nagamine, Tomoko

AU - Inagaki, Kyoko

AU - Fukuda, Izumi

AU - Iwabu, Masato

N1 - © 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 [email protected] 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 [email protected].

PY - 2024/7/2

Y1 - 2024/7/2

N2 - 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.

AB - 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.

KW - Humans

KW - Diabetes Mellitus, Type 1/genetics

KW - Adrenocorticotropic Hormone/deficiency

KW - Immune Checkpoint Inhibitors/adverse effects

KW - Male

KW - Female

KW - HLA Antigens/genetics

KW - Adrenal Insufficiency/genetics

KW - Adult

KW - Middle Aged

KW - Neoplasms/drug therapy

KW - Endocrine System Diseases

KW - Hypoglycemia

KW - Genetic Diseases, Inborn

U2 - 10.1093/ejendo/lvae081

DO - 10.1093/ejendo/lvae081

M3 - Article

C2 - 38917237

SN - 1479-683X

VL - 191

SP - 9

EP - 16

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 1

ER -

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

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

UN SDGs

Access to Document

Fingerprint

Cite this