TY  - JOUR
TI  - Autoantibody against UBE2E3 is a common biomarker for atherosclerotic diseases and digestive tract cancer
AU  - Hiwasa, Takaki
AU  - Yoshida, Yoichi
AU  - Kubota, Masaaki
AU  - Zhang, Bo-Shi
AU  - Li, Shu-Yang
AU  - Matsutani, Tomoo
AU  - Hirono, Seiichiro
AU  - Takemoto, Minoru
AU  - Iwase, Katsuro
AU  - Mine, Seiichiro
AU  - Machida, Toshio
AU  - Kobayashi, Yoshio
AU  - Takizawa, Hirotaka
AU  - Ito, Masaaki
AU  - Yajima, Satoshi
AU  - Shimada, Hideaki
AU  - Yokote, Koutaro
AU  - Higuchi, Yoshinori
PY  - 2025
JO  - Exploration of Cardiology
VL  - 3
SP  - 101258
DO  - 10.37349/ec.2025.101258
UR  - https://www.explorationpub.com/Journals/ec/Article/101258
AB  - Aim: Atherosclerosis and diabetes mellitus (DM) often lead to severe conditions, such as acute ischemic stroke (AIS), cardiovascular disease (CVD), and chronic kidney disease (CKD). Some cancers are also associated with atherosclerosis. Therefore, identifying novel autoantibody biomarkers associated with atherosclerosis-related conditions is crucial for improving early diagnosis and risk assessment. Methods: We used an array of 9,480 proteins to detect IgG antibodies in the serum of patients with atherosclerosis. Following this screening, we quantified the antibody levels using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) with recombinant antigen proteins. Results: Ubiquitin conjugating enzyme E2 E3 (UBE2E3) was identified as a candidate antigen recognized by IgG antibodies in the sera of individuals diagnosed with atherosclerosis. Compared with healthy donors, significantly higher serum antibody levels against UBE2E3 were found in patients with AIS, DM, CVD, CKD, esophageal cancer (EC), and gastric cancer (GC), but not in those with colorectal cancer (CRC). Receiver operating characteristic (ROC) analysis revealed that the higher areas under the ROC curves for anti-UBE2E3 antibodies were observed in DM- or nephrosclerosis-associated CKD than in the others. Spearman’s correlation analysis revealed that serum anti-UBE2E3 antibody (s-UBE2E3-Ab) levels were associated with the plaque score, maximum intima-media thickness, and cardio-ankle vascular index, which are typical indices of atherosclerosis and stenosis. In the survival analysis of GC and CRC, patients who were s-UBE2E3-Ab-positive had significantly poorer prognoses than patients who were s-UBE2E3-Ab-negative. The difference became more prominent when s-UBE2E3-Abs were combined with anti-differential screening-selected gene aberrant in neuroblastoma antibody (DAN-Ab) or sclerostin domain-containing protein 1 (SOSTDC1), which are bone morphogenetic protein (BMP) antagonists. Conclusions: The s-UBE2E3-Ab marker is highly associated with atherosclerosis-related diseases, such as AIS, CVD, DM, CKD, and digestive tract cancers, suggesting the involvement of BMP signals.
ER  -