scholarly journals Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu-Yang Li ◽  
Yoichi Yoshida ◽  
Eiichi Kobayashi ◽  
Masaaki Kubota ◽  
Tomoo Matsutani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Characteristic Curve ◽  
Serum Antibody ◽  
Area Under The Curve ◽  
Intima Media Thickness ◽  
Expression Cloning ◽  
Ischemic Attack ◽  
Antibody Levels

AbstractAtherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

scholarly journals Serum Anti-AP3D1 Antibodies Are Risk Factors for Acute Ischemic Stroke Related With Atherosclerosis

2021 ◽  
Author(s):  
Shu-Yang Li ◽  
Yoichi Yoshida ◽  
Eiichi Kobayashi ◽  
Masaaki Kubota ◽  
Tomoo Matsutani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Characteristic Curve ◽  
Serum Antibody ◽  
Area Under The Curve ◽  
Intima Media Thickness ◽  
Expression Cloning ◽  
Ischemic Attack ◽  
Antibody Levels

Abstract Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke, transient ischemic attack , diabetes mellitus (DM), cardiovascular disease , chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than that of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

scholarly journals Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Takaki Hiwasa ◽  
Hao Wang ◽  
Ken-ichiro Goto ◽  
Seiichiro Mine ◽  
Toshio Machida ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Serum Antibody ◽  
Protein Array ◽  
Cdna Libraries ◽  
Igg Antibodies ◽  
Serum Igg ◽  
Predictive Risk ◽  
Ischemic Attack ◽  
Antibody Levels

Abstract Background Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. Methods Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Results The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297–311 of DIDO1, 426–440 of FOXJ2, and 607–621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case–control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. Conclusions Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

scholarly journals Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masaaki Kubota ◽  
Yoichi Yoshida ◽  
Eiichi Kobayashi ◽  
Tomoo Matsutani ◽  
Shu-Yang Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Intima Media Thickness ◽  
Serum Levels ◽  
Acute Cerebral Infarction ◽  
Expression Cloning ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Ischemic Attack ◽  
Antibody Levels

AbstractThe presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

Optimal thresholds for ischemic penumbra predicted by computed tomography perfusion in patients with acute ischemic stroke treated with mechanical thrombectomy

2017 ◽  
Vol 10 (3) ◽  
pp. 279-284 ◽  
Author(s):  
Katsuharu Kameda ◽  
Junji Uno ◽  
Ryosuke Otsuji ◽  
Nice Ren ◽  
Shintaro Nagaoka ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cerebral Blood Volume ◽  
Mechanical Thrombectomy ◽  
Ct Perfusion ◽  
Characteristic Curve ◽  
Mean Transit Time ◽  
Area Under The Curve ◽  
Ischemic Penumbra ◽  
Optimal Thresholds

Background and purposeOptimal thresholds for ischemic penumbra detected by CT perfusion (CTP) in patients with acute ischemic stroke (AIS) have not been elucidated. In this study we investigated optimal thresholds for salvageable ischemic penumbra and the risk of hemorrhagic transformation (HT).MethodsA total of 156 consecutive patients with AIS treated with mechanical thrombectomy (MT) at our hospital were enrolled. Absolute (a) and relative (r) CTP parameters including cerebral blood flow (aCBF and rCBF), cerebral blood volume (aCBV and rCBV), and mean transit time (aMTT and rMTT) were evaluated for their value in detecting ischemic penumbra in each of seven arbitrary regions of interest defined by the major supplying blood vessel. Optimal thresholds were calculated by performing receiver operating characteristic curve analysis in 47 patients who achieved Thrombolysis In Cerebral Infarction (TICI) grade 3 recanalization. The risk of HT after MT was evaluated in 101 patients who achieved TICI grade 2b–3 recanalization.ResultsAbsolute CTP parameters for distinguishing ischemic penumbra from ischemic core were as follows: aCBF, 27.8 mL/100 g/min (area under the curve 0.82); aCBV, 2.1 mL/100 g (0.75); and aMTT, 7.30 s (0.70). Relative CTP parameters were as follows: rCBF, 0.62 (0.81); rCBV, 0.83 (0.87); and rMTT, 1.61 (0.73). CBF was significantly lower in areas of HT than in areas of infarction (aCBF, p<0.01; rCBF, p<0.001).ConclusionsCTP may be able to predict treatable ischemic penumbra and the risk of HT after MT in patients with AIS.

scholarly journals Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction

2020 ◽  
Author(s):  
Hao Wang ◽  
Hao Lu ◽  
Xiao-Meng Zhang ◽  
Ken-ichiro Goto ◽  
Eiichi Kobayashi ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Transient Ischemic Attack ◽  
Serum Antibody ◽  
Fumarate Hydratase ◽  
Multivariate Logistic Regression Analysis ◽  
Intima Media Thickness ◽  
Human Aortic Endothelial Cell ◽  
Atherosclerotic Stenosis ◽  
Ischemic Attack ◽  
Antibody Levels

Abstract Background: Ischemic stroke, such as transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and aCI are attempted. Methods: Candidate antigens recognized by IgG autoantibodies in the serum of 19 TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and aCI cohorts ( n = 285, 92 and 529). The antibody levels in the sera of the Japan Public Health Center-based Prospective Cohort Study (JPHC) from 1991 to 1993 was also examined. Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that the levels of anti-ALDOA antibodies (ALDOA-Abs) and anti-FH antibodies (FH-Abs) were both higher in patients with TIA or aCI than those in HDs ( P < 0.05). The levels of ALDOA-Abs [odds ratio (OR): 2.46, P = 0.0050] and FH-Abs (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis. The case-control study showed the levels of ALDOA-Abs (OR: 2.50, P < 0.01) and FH-abs (OR: 2.60, P < 0.01) were associated with risk of aCI. Correlation analysis demonstrated that both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease and habitual smoking. These antibody levels were also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. Conclusions: ALDOA-Abs and FH-Abs can serve as novel potential biomarkers for prediction of atherosclerotic TIA and aCI.

scholarly journals Carotid artery intima-media thickness in patients with acute ischemic stroke and its correlation with risk factors for atherosclerosis and/or stroke

2014 ◽  
Vol 6 (1) ◽  
pp. 22-27
Author(s):  
Shovan Kumar Das ◽  
Amit Sarkar ◽  
Subhraprakash Pramanik ◽  
Mitabha Bandyopadhyay ◽  
Koushik Mondal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Intima Media Thickness ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Media Thickness ◽  
Matched Study ◽  
Atherosclerotic Risk Factors

Introduction: Stroke is the second leading cause of mortality worldwide. Ischemic stroke is  more prevalent than hemorrhagic stroke and atherosclerosis is the major cause of ischemic stroke. The increased carotid artery intima-media thickness (CIMT) is considered to be useful indicator of early atherosclerosis. So, this study was aimed to correlate the relationship between atherosclerotic risk factors and intima-media thickness of carotid artery in patients with acute ischemic stroke. Material and Methods: In this cross-sectional study, 100 consecutive patients of acute ischemic stroke and 50 healthy relatives of patients as control were studied for presence of atherosclerotic risk factors and carotid artery intima?media thickness by B-mode Doppler ultrasonography.Results: In this age and sex matched study, higher CIMT measurement was found among patients of acute ischemic stroke than healthy controls (0.849 ± 0.196 vs 0.602 ± 0.092; p < 0.001). The CIMT was well correlated with smoking (Beta = 0.295; t = 5.728; 95% CI 0.088 to 0.181; p < 0.001); hypertension (Beta = 0.387; t = 6.518; CI 0.112 to 0.209; p < 0.001); di abetes (Beta = 0.237; t = 4.848; CI 0.074 to 0.175; p < 0.001); hypercholesterolemia (Beta = 0.292; t = 5.840; CI 0.096 to 0.195; p < 0.001), but not with age (p = 0.153). The CIMT was also found to be higher among acute ischemic stroke patients who were smoker, hypertensive, diabetic and hypercholesterolemic than non?smoker, normotensive, non-diabetic and normo-cholesterolemic respectively. Conclusion: The CIMT being indicator of atherosclerosis can be used as future predictor of ischemic stroke. DOI: http://dx.doi.org/10.3126/ajms.v6i1.10301 Asian Journal of Medical Sciences Vol.6(1) 2015 22-27

scholarly journals The Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios Predict Reperfusion and Prognosis after Endovascular Treatment of Acute Ischemic Stroke

2021 ◽  
Vol 11 (8) ◽  
pp. 696
Author(s):  
Sang-Hwa Lee ◽  
Min Uk Jang ◽  
Yerim Kim ◽  
So Young Park ◽  
Chulho Kim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Predictive Ability ◽  
Primary Outcome Measure ◽  
Lymphocyte Ratio ◽  
Prognostic Effect ◽  
Reperfusion Rate

Background: Studies assessing the prognostic effect of inflammatory markers of blood cells on the outcomes of patients with acute ischemic stroke treated with endovascular treatment (EVT) are sparse. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) affect reperfusion status in patients receiving EVT. Methods: Using a multicenter registry database, 282 patients treated with EVT were enrolled in this study. The primary outcome measure was unsuccessful reperfusion rate after EVT defined by thrombolysis in cerebral infarction grades 0–2a. Logistic regression analysis was performed to analyze the association between NLR/PLR and unsuccessful reperfusion rate after EVT. Results: Both NLR and PLR were higher in the unsuccessful reperfusion group than in the successful reperfusion group (p < 0.001). Multivariate analysis showed that both NLR and PLR were significantly associated with unsuccessful reperfusion (adjusted odds ratio (95% confidence interval): 1.11 (1.04–1.19), PLR: 1.004 (1.001–1.01)). The receiver operating characteristic curve showed that the predictive ability of both NLR and PLR was close to good (area under the curve (AUC) of NLR: 0.63, 95% CI (0.54–0.72), p < 0.001; AUC of PLR: 0.65, 95% CI (0.57–0.73), p < 0.001). The cutoff values of NLR and PLR were 6.2 and 103.6 for unsuccessful reperfusion, respectively. Conclusion: Higher NLR and PLR were associated with unsuccessful reperfusion after EVT. The combined application of both biomarkers could be useful for predicting outcomes after EVT.

scholarly journals Clinical Characteristics and Risk Factors of Lung Cancer-Associated Acute Ischemic Stroke

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Jiacai Lin ◽  
Siting Wu ◽  
Rui Xu ◽  
Qiang Shi ◽  
Chenglin Tian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Ischemic Stroke ◽  
Confidence Interval ◽  
Acute Ischemic Stroke ◽  
Survival Time ◽  
Clinical Characteristics ◽  
Area Under The Curve ◽  
Stage Iv ◽  
Neurological Deficits

Objective. To research the clinical characteristics and risk factors of lung cancer-associated acute ischemic stroke (LCA-AIS). Methods. Patients diagnosed with LCA-AIS, simple lung cancer, and simple AIS were enrolled. The primary information, laboratory results, tumor histopathology, neurological deficits, and survival time of the patients were collected and analyzed. Results. (1) In the LCA-AIS group, the pathology of 69.56% patients were adenocarcinoma, and the proportion of poorly differentiated patients was significantly more than that in moderately differentiated or highly differentiated. The number of stage IV lung cancer patients in the LCA-AIS group was significantly more common than in other stages. (2) 56.52% of patients with lung cancer were diagnosed before AIS, and the peak of AIS attack was 1–6 months after the diagnosis of lung cancer. (3) The independent risk factors of LCA-AIS were CYFRA-211 (OR 1.070; 95% confidence interval 1.005, 1.139; p=0.035), TT (OR 1.275; 95% confidence interval 1.089, 1.493; p=0.003), and Hct (OR 0.878; 95% confidence interval 0.779, 0.990; p=0.034), making ROC curve, suggesting the area under the curve is 0.871. (4) The neurological deficit of patients in the LCA-AIS group was similar to the simple AIS group and could not be identified by the severity of neurological deficits. (5) The median survival time of LCA-AIS group patients was five months (95% confidence interval 3.796, 6.204). There were statistical differences in survival time between LCA-AIS group and simple AIS group patients (p<0.001).Conclusions. The interaction between lung cancer and AIS may shorten patients’ life expectancy and worsen their quality of life.

scholarly journals Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Wang ◽  
Hao Lu ◽  
Xiao-Meng Zhang ◽  
Ken-ichiro Goto ◽  
Eiichi Kobayashi ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Transient Ischemic Attack ◽  
Serum Antibody ◽  
Fumarate Hydratase ◽  
Multivariate Logistic Regression Analysis ◽  
Intima Media Thickness ◽  
Human Aortic Endothelial Cell ◽  
Atherosclerotic Stenosis ◽  
Ischemic Attack ◽  
Antibody Levels

Abstract Background Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. Methods In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991–1993) were also examined. Results The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case–control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima–media thickness, which reflects atherosclerotic stenosis. Conclusions ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.

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