Endocrinology and Metabolism

Shintaro Iwama

2 Articles

Diabetes, Obesity and Metabolism
Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors: Hidefumi Inaba, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Takakazu Sugita, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, Takaaki Matsuoka; Endocrinol Metab. 2022;37(1):84-95. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1282

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Background
Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.
Methods
In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.
Results
Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.
Conclusion
Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Citations

Citations to this article as recorded by

A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome
John Marsiglio, Jordan P. McPherson, Magdalena Kovacsovics-Bankowski, Joanne Jeter, Christos Vaklavas, Umang Swami, Douglas Grossmann, Alyssa Erickson-Wayman, Heloisa P. Soares, Katie Kerrigan, Berit Gibson, Jennifer Anne Doherty, John Hyngstrom, Sheetal
Frontiers in Immunology.2023;[Epub] CrossRef
Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment
Almog Shalit, Panagiotis Sarantis, Evangelos Koustas, Eleni-Myrto Trifylli, Dimitris Matthaios, Michalis V. Karamouzis
Cancers.2023; 15(2): 375. CrossRef
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
Iñigo Les, Mireia Martínez, Inés Pérez-Francisco, María Cabero, Lucía Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Iñaki Elejalde, Grazyna Kochan, David Escors
Cancers.2023; 15(5): 1629. CrossRef
Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors
Hidefumi Inaba, Shuhei Morita, Daisuke Kosugi, Yuki Asai, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Masao Ota, Yuko Okudaira, Hiroyasu Nakatani, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, T
Frontiers in Immunology.2023;[Epub] CrossRef
Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study
Natsuko Hara, Hirotsugu Suwanai, Fumiyoshi Yakou, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa, Ryo Suzuki
Endocrine.2023; 81(3): 477. CrossRef
Autoimmunity in immune checkpoint inhibitor‐induced immune‐related adverse events: A focus on autoimmune skin toxicity and pneumonitis
Fiamma Berner, Lukas Flatz
Immunological Reviews.2023; 318(1): 37. CrossRef
Type 1 diabetes mellitus affected by potential toxicity from long-term use of nivolumab
Yuma Motomura, Shin Urai, Yushi Hirota, Naoki Takegawa, Hironori Bando, Masaaki Yamamoto, Hidenori Fukuoka, Masahiro Tsuda, Wataru Ogawa
Diabetology International.2023;[Epub] CrossRef
Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland
Ichiro Yamauchi, Takuro Hakata, Taku Sugawa, Daisuke Kosugi, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Norio Harada, Nobuya Inagaki
Endocrine Journal.2023; 70(10): 987. CrossRef
Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer
Majd Issa, Joy Tang, Yizhen Guo, Chris Coss, Thomas A. Mace, Jason Bischof, Mitch Phelps, Carolyn J Presley, Dwight H Owen
Expert Review of Anticancer Therapy.2022; 22(8): 861. CrossRef
Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors
Adithya Chennamadhavuni, Laith Abushahin, Ning Jin, Carolyn J. Presley, Ashish Manne
Frontiers in Immunology.2022;[Epub] CrossRef
Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice
Pablo Rodríguez de Vera-Gómez, Ana Piñar-Gutiérrez, Raquel Guerrero-Vázquez, Virginia Bellido, Cristóbal Morales-Portillo, María Pilar Sancho-Márquez, Pablo Espejo-García, Noelia Gros-Herguido, Gema López-Gallardo, María Asunción Martínez-Brocca, Alfonso
Journal of Diabetes Research.2022; 2022: 1. CrossRef

Miscellaneous
Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors: Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima; Endocrinol Metab. 2021;36(2):312-321. Published online April 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1007

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252 Download
10 Citations

Abstract PDF PubReader ePub

Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Citations

Citations to this article as recorded by

Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report
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Journal of Diabetes Investigation.2023; 14(1): 147. CrossRef
Case Report: A Rising Cause of New-Onset Endocrinopathies After Immunotherapy
Charity Tan, Sarah Hendricks, Kristina Hernandez, Martha Benavides, Rupinderjit Samra
The Journal for Nurse Practitioners.2023; 19(5): 104582. CrossRef
Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline
Xin Zhou, Shintaro Iwama, Tomoko Kobayashi, Masahiko Ando, Hiroshi Arima
The Journal of Clinical Endocrinology & Metabolism.2023; 108(10): e1056. CrossRef
Severe thyrotoxicosis induced by tislelizumab: a case report and literature review
Liman Huo, Chao Wang, Haixia Ding, Xuelian Shi, Bin Shan, Ruoying Zhou, Ping Liang, Juan Hou
Frontiers in Oncology.2023;[Epub] CrossRef
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tets
The Journal of Clinical Endocrinology & Metabolism.2022; 107(4): e1620. CrossRef
Biomarkers and risk factors for the early prediction of immune-related adverse events: a review
Ying Zhang, Xiaoling Zhang, Weiling Li, Yunyi Du, Wenqing Hu, Jun Zhao
Human Vaccines & Immunotherapeutics.2022;[Epub] CrossRef
Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle
Agnese Barnabei, Andrea Corsello, Rosa Maria Paragliola, Giovanni Maria Iannantuono, Luca Falzone, Salvatore Maria Corsello, Francesco Torino
Cancers.2022; 14(4): 1057. CrossRef
Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Xin Zhou, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Taka
The Journal of Clinical Endocrinology & Metabolism.2022; 107(10): e4115. CrossRef
Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors
Fabiana Pani, Yoshinori Yasuda, Sylvie T Rousseau, Kevin C Bermea, Solmaz Roshanmehr, Rulin Wang, Srinivasan Yegnasubramanian, Patrizio Caturegli, Luigi Adamo
Journal for ImmunoTherapy of Cancer.2022; 10(12): e005538. CrossRef
Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers
Anupam Kotwal, Mabel Ryder
Current Opinion in Endocrinology, Diabetes & Obesity.2021; 28(5): 517. CrossRef

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