Abstract
BackgroundSerum 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. MethodsWe 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. ResultsScreening 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. ConclusionSerum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI.
Highlights
To date, among the several factors that are recognized to underlie the progression of atherosclerosis are age, high blood pressure, hyperlipidemia, diabetes mellitus (DM), chronic kidney disease (CKD), smoking, and obesity [1]
DNA sequence analysis and search for homologous sequences in an National Center for Biotechnology Information (NCBI)-accessible database indicated that these isolated clones comprised 18 independent genes, including two genes related to heat shock proteins: DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1) and DnaJ heat shock protein family (Hsp40) member C2 (DNAJC2) (Table 2)
The clone isolated by the transient ischemic attack (TIA) sera contained base positions between 176 and 925 corresponding to amino acid positions between 1 and 224, whereas that isolated by the non-ST segment elevation acute coronary syndrome (NSTEACS) sera involved base positions between 55 and 2167 which covered the full-length coding sequence
Summary
Among the several factors that are recognized to underlie the progression of atherosclerosis are age, high blood pressure, hyperlipidemia, diabetes mellitus (DM), chronic kidney disease (CKD), smoking, and obesity [1]. Several studies identified antigens associated with atherosclerotic diseases including oxidized low-density lipoprotein (oxLDL) [12], apolipoprotein A-1 [13], and β2-glycoprotein I for atherosclerosis [14]; phospholipids [15], nardilysin [16] and heat shock proteins (Hsps) for CVD [17]; Hsp for stroke [18]; and insulin [19], glutamic acid decarboxylase (GAD) [20], and protein tyrosine phosphatase IA-2 [21,22] for DM. Serum antibody markers have been increasingly identified for cancer and autoimmune diseases and for atherosclerosis-related diseases such as acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD). Conclusion: Serum DNAJC2-Ab level may be useful for early detection of atherosclerotic lesions, which lead to AIS and AMI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
