PMID- 37957180
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20231116
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Nov 13
TI  - Human leukocyte antigen-DQ risk heterodimeric haplotypes of left ventricular 
      dysfunction in cardiac sarcoidosis: an autoimmune view of its role.
PG  - 19767
LID - 10.1038/s41598-023-46915-1 [doi]
LID - 19767
AB  - Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, 
      leading to heart abnormalities and patients with sarcoidosis with cardiac 
      involvements have poor prognoses. Due to the small number of patients, it is 
      difficult to stratify all patients of CS by human leukocyte antigen (HLA) 
      analysis. We focused on the structure of antigen-recognizing pockets in 
      heterodimeric HLA-class II, in addition to DNA sequences, and extracted 
      high-affinity combinations of antigenic epitopes from candidate autoantigen 
      proteins and HLA. Four HLA heterodimer-haplotypes 
      (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine 
      of the 10 patients had low left ventricular ejection fraction (< 50%). Fourteen 
      amino-acid sequences constituting four HLA anchor pockets encoded by the HLA 
      haplotypes were all common, suggesting DQA1*05:0X-DQB1*03:01 exhibit one group of 
      heterodimeric haplotypes. The heterodimeric haplotypes recognized eight epitopes 
      from different proteins. Assuming that autoimmune mechanisms might be activated 
      by molecular mimicry, we searched for bacterial species having peptide sequences 
      homologous to the eight epitopes. Within the peptide epitopes form the SLC25A4 
      and DSG2, high-homology sequences were found in Cutibacterium acnes and 
      Mycobacterium tuberculosis, respectively. In this study, we detected the risk 
      heterodimeric haplotypes of ventricular dysfunction in CS by searching for 
      high-affinity HLA-class II and antigenic epitopes from candidate cardiac 
      proteins.
CI  - (c) 2023. The Author(s).
FAU - Yamamoto, Hironori
AU  - Yamamoto H
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Miyashita, Yohei
AU  - Miyashita Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 
      miyashita.yohei@ncvc.go.jp.
AD  - Department of Legal Medicine, Osaka University Graduate School of Medicine, 
      Suita, Osaka, 565-0871, Japan. miyashita.yohei@ncvc.go.jp.
FAU - Minamiguchi, Hitoshi
AU  - Minamiguchi H
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Hosomichi, Kazuyoshi
AU  - Hosomichi K
AD  - Laboratory of Computational Genomics, School of Life Science, Tokyo University of 
      Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
FAU - Yoshida, Shohei
AU  - Yoshida S
AD  - Department of Cardiovascular Medicine, Kanazawa University Hospital, Kanazawa, 
      Ishikawa, 920-8641, Japan.
FAU - Kioka, Hidetaka
AU  - Kioka H
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Shinomiya, Haruki
AU  - Shinomiya H
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Nagata, Haruno
AU  - Nagata H
AD  - Department of Cardiovascular Medicine, University of the Ryukyus Graduate School 
      of Medicine, Nakagami, Okinawa, 903-0215, Japan.
FAU - Onoue, Kenji
AU  - Onoue K
AD  - Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Nara, 
      634-8522, Japan.
FAU - Kawasaki, Masato
AU  - Kawasaki M
AD  - Department of Cardiology, Osaka General Medical Center, Osaka, Osaka, 558-8558, 
      Japan.
FAU - Kuramoto, Yuki
AU  - Kuramoto Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Nomura, Akihiro
AU  - Nomura A
AD  - Innovative Research Center, Kanazawa University School of Medicine, Kanazawa, 
      Ishikawa, 920-8641, Japan.
FAU - Toma, Yuichiro
AU  - Toma Y
AD  - Department of Cardiovascular Medicine, University of the Ryukyus Graduate School 
      of Medicine, Nakagami, Okinawa, 903-0215, Japan.
FAU - Watanabe, Tetsuya
AU  - Watanabe T
AD  - Department of Cardiology, Osaka General Medical Center, Osaka, Osaka, 558-8558, 
      Japan.
FAU - Yamada, Takahisa
AU  - Yamada T
AD  - Department of Cardiology, Osaka General Medical Center, Osaka, Osaka, 558-8558, 
      Japan.
FAU - Ishihara, Yasuki
AU  - Ishihara Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
AD  - The 1st Department of Oral and Maxillofacial Surgery, Osaka University Graduate 
      School of Medicine, Suita, Osaka, 565-0871, Japan.
FAU - Nagata, Miho
AU  - Nagata M
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
AD  - Department of Medical Ethics and Medical Genetics, Kyoto University Graduate 
      School of Medicine, Kyoto, Kyoto, 606-8501, Japan.
FAU - Kato, Hisakazu
AU  - Kato H
AD  - Department of Medical Biochemistry, Osaka University Graduate School of Medicine, 
      Suita, Osaka, 565-0871, Japan.
FAU - Hakui, Hideyuki
AU  - Hakui H
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Saito, Yoshihiko
AU  - Saito Y
AD  - Department of Cardiovascular Medicine, Nara Prefecture Seiwa Medical Center, 
      Nara, Nara, 636-0802, Japan.
FAU - Asano, Yoshihiro
AU  - Asano Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 
      asano.yoshihiro@ncvc.go.jp.
AD  - Department of Genomic Medicine, National Cerebral and Cardiovascular Center, 
      Suita, Osaka, 564-8565, Japan. asano.yoshihiro@ncvc.go.jp.
FAU - Sakata, Yasushi
AU  - Sakata Y
AD  - Department of Cardiovascular Medicine, Osaka University Graduate School of 
      Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231113
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Epitopes)
RN  - 0 (Peptides)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Humans
MH  - Haplotypes
MH  - Stroke Volume
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - Ventricular Function, Left
MH  - HLA-DQ Antigens/genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - *Sarcoidosis/genetics
MH  - Epitopes
MH  - *Ventricular Dysfunction, Left/genetics
MH  - Peptides/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Gene Frequency
MH  - Alleles
MH  - Genetic Predisposition to Disease
PMC - PMC10643531
COIS- The authors declare no competing interests.
EDAT- 2023/11/14 00:42
MHDA- 2023/11/15 06:43
PMCR- 2023/11/13
CRDT- 2023/11/13 23:20
PHST- 2022/12/13 00:00 [received]
PHST- 2023/11/07 00:00 [accepted]
PHST- 2023/11/15 06:43 [medline]
PHST- 2023/11/14 00:42 [pubmed]
PHST- 2023/11/13 23:20 [entrez]
PHST- 2023/11/13 00:00 [pmc-release]
AID - 10.1038/s41598-023-46915-1 [pii]
AID - 46915 [pii]
AID - 10.1038/s41598-023-46915-1 [doi]
PST - epublish
SO  - Sci Rep. 2023 Nov 13;13(1):19767. doi: 10.1038/s41598-023-46915-1.