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-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 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.

Serum Anti-AP3D1 Antibodies Are Broad-Spectrum Biomarkers for Atherosclerosis, Acute Ischemic Stroke, Cardiovascular Disease, Diabetes Mellitus, Chronic Kidney Disease, and Digestive Organ Cancer

2020 ◽  
Author(s):  
Shu-Yang Li ◽  
Yoichi Yoshida ◽  
Eiichi Kobayashi ◽  
Masaaki Kubota ◽  
Tomoo Matsutani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Acute Ischemic Stroke ◽  
Broad Spectrum ◽  
Serum Antibody ◽  
Digestive Organ ◽  
Antibody Levels

Abstract Background: Atherosclerosis has been considered as the main cause of morbidity, mortality, premature incapacity, and disability worldwide. For early and sensitive diagnosis, development of novel biomarkers is expected and of significant practical importance.Methods: The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning (SEREX). Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen.Results: SEREX screening has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. As per the results of AlphaLISA, it was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack (TIA), diabetes mellitus (DM), cardiovascular disease (CVD), 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 noted to be 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 Japan Public Health Center-based Prospective Study results have verified that the serum antibody levels against AP3D1 showed significantly higher odds ratios with the risk of AIS for persons with the third quartiles and the highest quartiles versus the lowest quartile, indicating that this antibody marker is deemed useful as risk factors for AIS.Conclusions: Serum anti-AP3D1 antibodies, which are broad-spectrum biomarkers of atherosclerotic diseases and digestive organ cancers, could be useful in predicting the onset of AIS.

Abstract TP251: Onset-to-Door Times and Means of Transportation for Acute Ischemic Stroke Patients Attending a Public Hospital in Bogota DC, Colombia. Is an Ambulance the Fastest Way to Reach the Hospital?

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Javier Vicini-Parra ◽  
Jenny Ospina ◽  
Cristian Correa ◽  
Natalia Gomez ◽  
Stephania Bohorquez ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Public Transportation ◽  
Public Hospital ◽  
Descriptive Analysis ◽  
First Year ◽  
Stroke Patients ◽  
Health Authorities ◽  
Public Health Authorities ◽  
Ischemic Attack

Introduction: A prospective stroke database was implemented as part of a still-growing comprehensive stroke centre (CSC). This CSC is located within a referral public hospital (Hospital Occidente de Kennedy) in Bogota DC, Colombia , that serves 2.3 million people of mainly low economic income. In this abstract, we present the data pertaining patients who were thrombolysed in our institution during the first year of data collection, and specify onset-to-door (OTD) times as they relate to the means of transportation used. Hypothesis: Acute stroke patients who arrive in ambulance have the shortest onset-to-door times. Methods: Printed forms were filled for every patient who arrived with diagnosis of acute ischemic stroke (AIS) or transient ischemic attack (TIA). Data was transcribed to an electronic database (Numbers, Apple Inc.) and analyzed with SPSS Statistics version 23 (IBM Corporation). A retrospective descriptive analysis was performed for central tendency and dispersion measures. Results: Since August 1st 2014 until July 31st 2015, 39 patients (17.7% of AIS patients) were thrombolysed. Mean onset-to-door times are shown in table 1. Prenotification was received for only 1 patient. All patients came from their homes. Conclusions: Almost half of our thrombolysed patients arrived in taxi to our institution. Taxi was the fastest means of transportation, ambulance was the slowest and private cars were in the middle of those. This confirmed our suspicion that the state-owned emergency medical services (SEMD) are suboptimal and that stroke patients prefer to use public transportation rather than SEMD. This should warn public health authorities on he urgent need to improve our SEMD. In the meantime, this finding prompts us to include taxi drivers in our periodic stroke campaigns.

Intensive Versus Moderate Statin Therapy Discontinuation in Patients With Acute Ischemic Stroke or Transient Ischemic Attack

2018 ◽  
Vol 40 (12) ◽  
pp. 2041-2049
Author(s):  
Huai Wu Yuan ◽  
Ren Jie Ji ◽  
Ya Jie Lin ◽  
Han Feng Chen ◽  
Guo Ping Peng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Statin Therapy ◽  
Transient Ischemic Attack ◽  
Therapy Discontinuation ◽  
Ischemic Attack
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