Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases
Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases
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DOI：
10.1016/j.heliyon.2020.e04661
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发表时间：
2020-08-01
期刊：
影响因子：
4
通讯作者：
Hiwasa, Takaki
中科院分区：
文献类型：
--
作者：
Yoshida, Yoichi;Zhang, Xiao-Meng;Hiwasa, Takaki
背景资料：血清抗体标记物不仅越来越多地被鉴定用于癌症和自身免疫性疾病，而且用于动脉粥样硬化相关疾病，如急性缺血性中风（AIS）、急性心肌梗死（AMI）、糖尿病（DM）和慢性肾病（CKD）。短暂性脑缺血发作（TIA）和非ST段抬高急性冠状动脉综合征（NSTEACS）的生物标志物是潜在的有用的检测早期阶段的动脉粥样硬化的变化对AIS和AMI，either.Methods：我们利用重组cDNA表达克隆（SEREX），使用人主动脉内皮细胞cDNA噬菌体文库和TIA或NSTEACS患者的血清抗原的血清学鉴定。结果：筛选TIA患者血清，筛选出DnaJ热休克蛋白家族（Hsp 40）成员C2（DNAJC 2）作为候选抗原，并通过SEREX筛选获得NSTEACS患者血清中的DnaJ热休克蛋白C2。验证队列显示TIA或AIS患者血清中的DNAJC 2抗体（DNAJC 2-Ab）水平显著高于健康供体（HD）。多变量逻辑回归分析表明，TIA和AIS的DNAJC 2-Ab水平的预测比值比（OR）分别为2.54（95%置信区间[CI]：1.36-4.74，p = 0.0034）和2.14（95% CI：1.39-3.30，p = 0.0005）。结论：血清DNAJC 2-Ab水平可用于早期发现导致AIS和AMI的动脉粥样硬化病变。
Background: Serum antibody markers have been increasingly identified not only for cancer and autoimmune diseases but also for atherosclerosis-related diseases such as acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD). Biomarkers for transient ischemic attack (TIA) and non-ST segment elevation acute coronary syndrome (NSTEACS) are potentially useful for detection of early phase of atherosclerotic changes against AIS and AMI, respectively.Methods: We utilized serological identification of antigens by recombinant cDNA expression cloning (SEREX) using a human aortic endothelial cell cDNA phage library and sera from patients with TIA or NSTEACS. Serum antibody levels were measured by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using purified recombinant antigens.Results: Screening of sera from patients with TIA identified DnaJ heat shock protein family (Hsp40) member C2 (DNAJC2) as a candidate antigen, which was also isolated by SEREX screening using sera of patients with NSTEACS. The validation cohort revealed significantly higher DNAJC2 antibody (DNAJC2-Ab) levels in the sera of patients with TIA or AIS than those in healthy donors (HDs). Multivariate logistic regression analysis indicated that the predictive odds ratios (OR) of DNAJC2-Ab levels for TIA and AIS were 2.54 (95% confidence interval [CI]: 1.36-4.74, p = 0.0034) and 2.14 (95% CI: 1.39-3.30, p = 0.0005), respectively. Serum DNAJC2-Ab levels were also higher in patients with AMI, DM, and CKD than those in HDs.Conclusion: Serum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI.