Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors.

Abstract

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.

• Authors: 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
• Journal: Endocrinology and metabolism (Seoul, Korea) (Endocrinol Metab (Seoul)) Vol. 37 Issue 1 Pg. 84-95 (02 2022) ISSN: 2093-5978 [Electronic] Korea (South)
• PMID: 35255603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Immune Checkpoint Inhibitors

Topics

• Alleles
• Biomarkers
• Diabetes Mellitus, Type 1 (genetics)
• Female
• Gene Frequency
• Humans
• Immune Checkpoint Inhibitors
• Male