HLA analysis of immune checkpoint inhibitor-induced and idiopathic isolated ACTH deficiency

Purpose Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorti...

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Bibliographic Details
Published in:Pituitary 2022-08, Vol.25 (4), p.615-621
Main Authors: Ono, Mayo, Fukuda, Izumi, Nagao, Mototsugu, Tomiyama, Keiko, Okazaki-Hada, Mikiko, Shuto, Yuki, Kobayashi, Shunsuke, Yamaguchi, Yuji, Nagamine, Tomoko, Nakajima, Yasushi, Inagaki-Tanimura, Kyoko, Sugihara, Hitoshi
Format: Article
Language:English
Subjects:
Adrenocorticotropic hormone
Antibodies
Antigens
Apoptosis
Bladder cancer
Body mass index
Body weight loss
Diabetes
Disease
DQA1 protein
Drb1 protein
Endocrinology
Histocompatibility antigen HLA
Human Physiology
Immune checkpoint
Kidney cancer
Linkage disequilibrium
Medicine
Medicine & Public Health
Melanoma
Pathophysiology
Patients
Rare diseases
Thyroid gland
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Summary:Purpose Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorticotropic hormone deficiency (IAD) and idiopathic IAD (IIAD). Design and methods: Clinical features and HLA frequencies were compared among 13 patients with ICI-induced IAD, 8 patients with IIAD, and healthy controls. HLA frequencies of healthy controls were adopted from a HLA database of Japanese population. Results Age and body mass index were higher, while the rate of weight loss was lower, in patients with ICI-induced IAD than in those with IIAD. No HLA alleles had a significantly higher frequency in patients with ICI-induced IAD than in healthy controls, whereas the frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02, and DQB1*03:03 were significantly higher in patients with IIAD than in healthy controls. Conclusions ICI-induced IAD and IIAD were different in terms of HLA frequencies. There were no specific HLAs related to ICI-induced IAD, whereas several HLAs in strong linkage disequilibrium were associated with IIAD. This might suggest that the two diseases have different pathological mechanisms. HLAs unique to IIAD may be helpful in predicting its pathophysiology.
ISSN:1386-341X
1573-7403
DOI:10.1007/s11102-022-01231-1