PMID- 35255603
OWN - NLM
STAT- MEDLINE
DCOM- 20220315
LR  - 20220329
IS  - 2093-5978 (Electronic)
IS  - 2093-596X (Print)
IS  - 2093-596X (Linking)
VI  - 37
IP  - 1
DP  - 2022 Feb
TI  - Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by 
      Immune-Checkpoint Inhibitors.
PG  - 84-95
LID - 10.3803/EnM.2021.1282 [doi]
AB  - 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.
FAU - Inaba, Hidefumi
AU  - Inaba H
AD  - Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical 
      Center, Wakayama, Japan.
AD  - The First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
FAU - Kaido, Yosuke
AU  - Kaido Y
AD  - Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical 
      Center, Wakayama, Japan.
FAU - Ito, Saya
AU  - Ito S
AD  - Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical 
      Center, Wakayama, Japan.
FAU - Hirobata, Tomonao
AU  - Hirobata T
AD  - Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical 
      Center, Wakayama, Japan.
FAU - Inoue, Gen
AU  - Inoue G
AD  - Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical 
      Center, Wakayama, Japan.
FAU - Sugita, Takakazu
AU  - Sugita T
AD  - Department of Respiratory Medicine, Japanese Red Cross Wakayama Medical Center, 
      Wakayama, Japan.
FAU - Yamamoto, Yuki
AU  - Yamamoto Y
AD  - Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
FAU - Jinnin, Masatoshi
AU  - Jinnin M
AD  - Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
FAU - Kimura, Hiroaki
AU  - Kimura H
AD  - Department of Pharmaceutical Health Sciences, Kyushu University of Health and 
      Welfare, Nobeoka, Japan.
FAU - Kobayashi, Tomoko
AU  - Kobayashi T
AD  - Department of Endocrinology and Diabetes, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Iwama, Shintaro
AU  - Iwama S
AD  - Department of Endocrinology and Diabetes, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Arima, Hiroshi
AU  - Arima H
AD  - Department of Endocrinology and Diabetes, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Matsuoka, Takaaki
AU  - Matsuoka T
AD  - The First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220228
PL  - Korea (South)
TA  - Endocrinol Metab (Seoul)
JT  - Endocrinology and metabolism (Seoul, Korea)
JID - 101554139
RN  - 0 (Biomarkers)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Alleles
MH  - Biomarkers
MH  - *Diabetes Mellitus, Type 1/genetics
MH  - Female
MH  - Gene Frequency
MH  - Humans
MH  - Immune Checkpoint Inhibitors
MH  - Male
PMC - PMC8901959
OTO - NOTNLM
OT  - Biomarkers
OT  - Chemokines
OT  - Cytokines
OT  - Diabetes mellitus, type 1
OT  - Immune checkpoint inhibitors
OT  - Immune-related adverse events
COIS- CONFLICTS OF INTEREST Shintaro Iwama received personal fees from Ono 
      Pharmaceutical Co. Ltd., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., 
      and MSD K.K. outside of this study. Hiroshi Arima received grants from Ono 
      Pharmaceutical Co. Ltd., MSD K.K., and Chugai Pharmaceutical Co. Ltd., and 
      personal fees from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, and MSD 
      K.K. outside of this study. The other authors declare no conflicts of interest.
EDAT- 2022/03/09 06:00
MHDA- 2022/03/16 06:00
PMCR- 2022/02/01
CRDT- 2022/03/08 00:05
PHST- 2021/10/01 00:00 [received]
PHST- 2021/12/27 00:00 [accepted]
PHST- 2022/03/08 00:05 [entrez]
PHST- 2022/03/09 06:00 [pubmed]
PHST- 2022/03/16 06:00 [medline]
PHST- 2022/02/01 00:00 [pmc-release]
AID - EnM.2021.1282 [pii]
AID - enm-2021-1282 [pii]
AID - 10.3803/EnM.2021.1282 [doi]
PST - ppublish
SO  - Endocrinol Metab (Seoul). 2022 Feb;37(1):84-95. doi: 10.3803/EnM.2021.1282. Epub 
      2022 Feb 28.