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.

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

2020 ◽  
Author(s):  
Hao Hao Wang ◽  
Hao Hao Lu ◽  
Xiao-Meng Xiao-Meng Zhang ◽  
Ken-ichiro Ken-ichiro Goto ◽  
Eiichi Eiichi Kobayashi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Transient Ischemic Attack ◽  
Case Control Study ◽  
Smoking Habit ◽  
Case Control ◽  
Human Aortic Endothelial Cell ◽  
Ischemic Attack ◽  
Antibody Levels ◽  
Control Study

Abstract Background and Purpose: Ischemic stroke, such as Transient ischemic attack (TIA) and cerebral infarction (CI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and CI is attempted.Methods: Candidate antigens recognized by IgG autoantibodies in the sera of nineteen 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 CI cohorts (n = 285, 92 and 529). A case-control study nested within the Japan Public Health Center-based Prospective Cohort Study (JPHC) was performed.Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that anti-ALDOA and anti-FH antibody levels were both higher in TIA or CI patients than in HDs ( P < 0.0001). The levels of anti-ALDOA [Odds ratio (OR): 2.46, P = 0.005] and anti-FH (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis, similar results were found in CI. The case-control study showed the levels of anti-ALDOA (OR: 2.50, P < 0.01) and anti-FH (OR: 2.60, P < 0.01) were associated with risk of CI. Spearman’s correlation analysis demonstrated an association between the anti-ALDOA and anti-FH levels and risk factors of ischemic stroke, such as age, smoking habit, coronary heart disease, and hypertension.Conclusions: Anti-ALDOA and anti-FH antibodies can serve as novel potential biomarkers for prediction of TIA and CI.

Cross Correlation Statistical Study of Biomarker for Cerebral Infarction

2019 ◽  
Vol 9 (6) ◽  
pp. 1272-1277
Author(s):  
Hao Lu ◽  
Mingjie Mai ◽  
Min Guan ◽  
Kazuo Sugimoto ◽  
Shikai Wu ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Statistical Study ◽  
Smoking Habit ◽  
Serum Antibody ◽  
Human Aortic Endothelial Cell ◽  
Cerebrovascular Disorder ◽  
Healthy Donors ◽  
Homogeneous Assay ◽  
Ischemic Attack ◽  
Antibody Levels

Cerebral infarction (CI) is the most common cerebrovascular disorder with high fatality and disability rates worldwide, and transient ischemic attack (TIA) is a warning of CI, and early diagnosis and intervention of TIA are very important for the prevention of CI. We screened a human aortic endothelial cell cDNA library using serum from TIA patients to obtain lysosomal-associated membrane protein 1 (LAMP1) antigen. Amplified luminescent proximity homogeneous assay-linked immunosorbentassay (AlphaLISA) revealed that the antibody levels against LAMP1 were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (HDs) (P < 0.01) by examined in three independent cohorts (77 and 158 in the TIA and acute aCI patient cohorts, respectively, and 122 in HD cohort used as normal control). Spearman correlation analysis demonstrated that LAMP1-Abs levels were positively correlated with cigarette smoking habit. The serum antibody levels against LAMP1 could potentially serve as a useful biomarker for early detection of TIA or predicting of the onset of CI.

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-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.

scholarly journals Anti-KIAA0513 Antibody as a Broad-spectrum Biomarker of Mortal Atherosclerotic and Cancerous Diseases

2021 ◽  
Author(s):  
Takaki Hiwasa ◽  
Shu-Yang Li ◽  
Masaaki Kubota ◽  
Bo-Shi Zhang ◽  
Yoichi Yoshida ◽  
...  
Keyword(s):  
Sleep Apnea Syndrome ◽  
Serum Antibody ◽  
Intima Media Thickness ◽  
Roc Curves ◽  
Protein Array ◽  
Serum Samples ◽  
Plaque Score ◽  
Obstructive Sleep ◽  
Ischemic Attack ◽  
Antibody Levels

Abstract Background: Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD), and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders such as angiogenesis and atherosclerosis, and DM is a risk factor for certain cancers. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected by a common biomarker.Methods: We employed the protein array method for the initial screening of antigens and employed the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) to evaluate antibody levels in serum samples.Results: The protein array identified KIAA0513 as an antigen recognized by serum IgG antibodies in the sera of patients with atherosclerosis. We then prepared recombinant glutathione S-transferase-fused KIAA0513 protein. AlphaLISA showed significantly higher serum antibody levels against KIAA0513 protein in patients with AIS, transient ischemic attack, DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD, and solid cancers, such as esophageal, gastric, colon, lung, and breast cancer, than in healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were for esophageal cancer, nephrosclerosis-type CKD, and DM. Spearman’s correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis.Conclusion: Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD, and solid cancers and might reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

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 Application of Multimodal MRI in Cerebral Infarction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
Mengjiao Wei
Keyword(s):  
Early Detection ◽  
Cerebral Infarction ◽  
Transient Ischemic Attack ◽  
Clinical Treatment ◽  
Intracranial Artery ◽  
Ischemic Penumbra ◽  
Infarct Area ◽  
Intracranial Artery Stenosis ◽  
Multimodal Mri ◽  
Ischemic Attack

 Symptomatic atherosclerotic intracranial artery stenosis often causes ischemic cerebral infarction or transient ischemic attack in the stenosis area. Early detection of cerebral infarction and evaluation of ischemic penumbra and hemodynamics in the infarct area Information plays an extremely important role in clinical treatment and prognosis. This article briefly introduces the application of multimodal MRI in cerebral infarction.

Abstract WP49: Distal Hyperintense Vessels Were not a Predictor of Large Vessel Occlusion in Patients With Transient Ischemic Attack

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Marcelo M de Figueiredo ◽  
Marcela R Vazzoller ◽  
Edson Amaro Jr ◽  
Renata A Miranda ◽  
Gisele S Silva
Keyword(s):  
Transient Ischemic Attack ◽  
Surrogate Marker ◽  
Multivariate Logistic Regression Analysis ◽  
Clinical Information ◽  
Large Vessel ◽  
Arterial Stenosis ◽  
Large Artery ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Ischemic Attack

Introduction: Distal hyperintense vessels (DHV) detected by FLAIR imaging are not uncommon in patients with acute ischemic stroke. The presence of DHV and its predictors has been scarcely evaluated in patients with transient ischemic attack (TIA), being associated to the presence of large vessel occlusion in such patients. We assessed the hypothesis that DHV are frequent in patients with TIA and do correlate with relevant clinical and neuroimaging characteristics. Methods: We evaluated a database of consecutive patients admitted with TIA from February 2009 to June 2012 who had undergone magnetic resonance imaging within 30 h of symptoms onset and intracranial and extracranial vascular imaging. We analyzed the relationship between DHV, clinical presentation, risk factors, neuroimaging characteristics and large artery stenosis or occlusion. DHV signals were defined on FLAIR images as focal, linear or serpentine, hyperintense signals relative to gray matter. Two neuroradiologists blinded to clinical information reached consensus regarding the presence of DHV. Results: Seventy-two TIA patients were enrolled. The median time from symptoms onset to MRI was 8:39 h [4:21, 14:13]. DHV signals on FLAIR images were present in 12 (16.7 %) patients. The overall agreement between examiners was good (k 0.67). Patients with DHV had more atrial fibrillation (AF) than those without (41.7% versus 21.7%, p=0.05) and a trend towards more congestive heart failure (CHF) (8.3% versus 1.7%, p=0.2) and diabetes (41.7% versus 21.7%, p=0.1). There were no differences in the frequency of intracranial or cervical arterial stenosis, cerebral microbleeds and white matter abnormalities in patients with and without DHV. In a multivariate logistic regression analysis, only AF had a trend to be a predictor of DHV (OR=4.24, p=0.1). The statistical model to predict DHV including AF, diabetes, and CHF had a moderate fit in terms of discrimination (c statistic=0.62) Conclusion: DHV signals on FLAIR images occur in patients with TIA and might correlate with clinical variables like AF and not only with large vessel occlusion as previously described. The presence of DVH in patients with TIA and AF might be a surrogate marker for a previous large vessel occlusion spontaneously recanalized.

scholarly journals Leukoaraiosis Is a Chronic Atherosclerotic Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Einor Ben-Assayag ◽  
Milija Mijajlovic ◽  
Shani Shenhar-Tsarfaty ◽  
Irena Bova ◽  
Ludmila Shopin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Multivariate Logistic Regression Analysis ◽  
White Matter Lesions ◽  
Intima Media Thickness ◽  
Atherosclerotic Disease ◽  
Stroke Patients ◽  
Vascular Events ◽  
Tight Association ◽  
Ischemic Attack

Background and Purpose.White matter changes (WMCs), or leukoaraiosis (LA), are associated with increased age, hypertension, diabetes mellitus, and history of stroke. Although several lines of evidence suggest a role of atherosclerosis in atherothrombotic vascular events, their involvement in LA remains to be determined. Our study examines this association in ischemic stroke patients.Methods.One hundred and seventy consecutive ischemic stroke or transient ischemic attack (TIA) patients were included. All patients underwent brain computed tomography (CT) with assessment of the extension and severity of WMCs, carotid arteries duplex scan with measurements of intima-media thickness (IMT) and plaques.Results.Seventy-two patients (42.4%) were found to have white matter lesions, of whom 28.8% had advanced LA. Mean IMT was significantly higher in patients with LA and with advanced LA (P=0.002,P=0.003, resp.). In addition, LA and LA severity were associated with existence of carotid plaque (P=0.007,P=0.004, resp.). In multivariate logistic regression analysis, including all vascular risk factors, LA was found to be associated with age and IMT.Conclusion.This study reinforces the tight association between LA and carotid atherosclerosis in ischemic stroke patients. We conclude that a chronic atherosclerotic disease underlies the pathophysiology of leukoaraiosis and its progression.

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