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.

scholarly journals FAKTOR-FAKTOR RISIKO STROKE PADA PENYAKIT GINJAL KRONIK STADIUM V YANG MENJALANI HEMODIALISIS

2018 ◽  
Vol 35 (2) ◽  
Author(s):  
Susanti Dwi Ariani ◽  
Dodik Tugasworo ◽  
Maria Imakulata Widiastuti Samekto
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Multivariate Analysis ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Case Group ◽  
Chi Square ◽  
Stroke Incidence ◽  
Incidence And Mortality

RISK FACTORS OF STROKE IN STAGE V CHRONIC KIDNEY DISEASE WHO UNDERWENT HEMODIALYSISABSTRACTIntroduction: Chronic kidney disease (CKD) and end-stage renal disease are associated with a significantly in- creased risk of stroke. Incidence and mortality of stroke in CKD patients is higher rather than among the general popula- tion. Stroke in hemodialysis patients is also associated with high mortality.Aims: To analyze risk factors that have a relationship with the occurrence of stroke in patients with stage V CKD who underwent hemodialysis in Dr. Kariadi Hospital, Semarang.Method: A case control with retrospective cohort study of patients diagnosed with stage V CKD undergoing hemo- dialysis in Dr. Kariadi Hospital, Semarang, from March 2016 to August 2017. Subject was divided into case group, who experienced stroke, and control group, who did not experience stroke. Bivariate analysis was performed with Chi-square test, multivariate analysis with logistic regression test and rasio Odds.Results: There were 140 subjects with stage V CKD, 70 subjects in each groups. In case group, 85.7% experienced ischemic stroke while the rest hemorrhagic stroke. The duration of hemodialysis was related to the incidence of stroke. In multivariate analysis, patients with diabetes mellitus were more likely to have a stroke by 0.14 times compared to patients who did not have diabetes mellitus, and patients who underwent hemodialysis >12 months, were more likely to have a stroke 4.05 times greater than patients who underwent hemodialysis <12 months.Discussion: There is a relationship between diabetes mellitus and duration of hemodialysis with the occurrence of ischemic stroke, in stage V CKD patients who underwent hemodialysis.Keywords: Chronic kidney disease, hemodialysis, strokeABSTRAKPendahuluan: Penyakit ginjal kronik (PGK) dan penyakit ginjal stadium akhir terkait dengan peningkatan risiko yang signifikan dari stroke. Insiden dan mortalitas stroke pada pasien PGK lebih tinggi dibandingkan populasi umum. Stroke pada pasien dialisis juga dihubungkan dengan mortalitas yang tinggi.Tujuan: Untuk menganalisis faktor-faktor risiko yang memengaruhi terjadinya stroke pada pasien dengan PGK stadium V yang menjalani hemodialisis (HD) di RSUP Dr. Kariadi, Semarang.Metode: Penelitian kasus kontrol dengan pendekatan kohort retrospektif terhadap pasien penyakit ginjal kronik stadium V yang menjalani HD di RSUP Dr. Kariadi, Semarang dari bulan Maret 2016 hingga Agustus 2017. Subjek dibagi ke dalam kelompok kasus, yaitu yang mengalami stroke dan kelompok kontrol yang tidak mengalami stroke. Dilakukan analisis bivariat dengan uji Chi-square dan analisis multivariat dengan uji regresi logistik serta rasio Odds.Hasil: Didapatkan 140 subjek dengan PGK stadium V yang masing-masing kelompok terdiri dari 70 orang. Pada kelompok kasus, sebanyak 85,7% adalah stroke iskemik dan sisanya stroke hemoragik. Lama HD berhubungan dengan kejadian stroke. Pada uji multivariat, subjek yang menderita diabetes melitus (DM) berisiko mengalami stroke sebesar 0,14 kali dibandingkan yang tidak DM dan subjek yang menjalani HD >12 bulan berisiko mengalami stroke 4,05 kali lebih besar dibandingkan yang menjalani HD <12 bulan.Diskusi: Terdapat pengaruh faktor risiko DM dan lama hemodialisis terhadap kejadian stroke iskemik pada pasien PGK stadium V yang menjalani HD.Kata kunci: Hemodialisis, penyakit ginjal kronik, stroke

scholarly journals Prescribing Trend of Antirheumatic Drugs in Taiwan and Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Chien-Ying Lee ◽  
Chih-Jaan Tai ◽  
Ya-Fang Tsai ◽  
Yu-Hsiang Kuan ◽  
Chiu-Hsiang Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Control Group ◽  
Research Database ◽  
Antirheumatic Drugs ◽  
Prescribing Trend

We aimed to investigate the prescribing trend of antirheumatic drugs and assess the risk of cardiovascular disease in patients with rheumatoid arthritis in Taiwan. This study was a retrospective cohort study, conducted based on the Taiwan National Health Insurance Research Database. The study subjects were 15,366 new rheumatoid arthritis patients from 2003 to 2010. To avoid selection bias, we applied propensity score matching to obtain general patients, as the control group. Cox proportional hazard model was used to evaluate the risk of cardiovascular disease in rheumatoid arthritis patients. The most common prescriptions of rheumatoid arthritis were nonsteroidal anti-inflammatory drugs. After controlling for related variables, rheumatoid arthritis patients had a higher risk of cardiovascular disease than general patients (adjusted hazard ratio [aHR] = 1.31; 95% confidence interval [CI]: 1.23-1.39). Age was the most significantly associated risk factor with the cardiovascular disease. Other observed risk factors for cardiovascular disease included hypertension (aHR = 1.57, 95% CI: 1.48-1.65), diabetes mellitus (aHR = 1.47, 95% CI: 1.38-1.57), and chronic kidney disease (aHR = 1.48, 95% CI: 1.31-1.66). Patients with rheumatoid arthritis indeed had a higher risk of incident cardiovascular diseases. Besides, age, hypertension, diabetes mellitus, and chronic kidney disease were also associated with a higher risk of cardiovascular disease.

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 Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

2017 ◽  
Vol 312 (4) ◽  
pp. F673-F681 ◽  
Author(s):  
Andrés Carmona ◽  
Maria L. Agüera ◽  
Carlos Luna-Ruiz ◽  
Paula Buendía ◽  
Laura Calleros ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Prognostic Markers ◽  
Plasma Concentrations ◽  
Endothelial Damage ◽  
Inflammatory State ◽  
Monocyte Subpopulations ◽  
Elisa Data

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

scholarly journals High blood pressure in acute ischemic stroke and clinical outcome

2009 ◽  
Vol 1 (1) ◽  
pp. 1 ◽  
Author(s):  
Yasuhiro Manabe ◽  
Syoichiro Kono ◽  
Tomotaka Tanaka ◽  
Hisashi Narai ◽  
Nobuhiko Omori
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Acute Ischemic Stroke ◽  
High Blood Pressure ◽  
Pressure Measurements ◽  
Pressure Group ◽  
History Of

This study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome. We studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes, employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission. High blood pressure was defined when the mean of at least 2 blood pressure measurements was ≥200 mmHg systolic and/or ≥110 mmHg diastolic at 6 to 24 hours after admission or ≥180 mmHg systolic and/or ≥105 mmHg diastolic at 24 to 36 hours after admission. The high blood pressure group was found to include 16% of the patients. Age, sex, diabetes mellitus, hypercholesterolemia, atrial fibrillation, ischemic heart disease, stroke history, carotid artery stenosis, leukoaraiosis, NIH Stroke Scale (NIHSS) on admission and mortality were not significantly correlated with either the high blood pressure or non-high blood pressure group. High blood pressure on admission was significantly associated with a past history of hypertension, kidney disease, the modified Rankin Scale (mRS) on discharge and the length of stay. On logistic regression analysis, with no previous history of hypertension, diabetes mellitus, atrial fibrillation, and kidney disease were independent risk factors associated with the presence of high blood pressure [odds ratio (OR), 1.85 (95% confidence interval (CI): 1.06-3.22), 1.89 (95% CI: 1.11-3.22), and 3.31 (95% CI: 1.36-8.04), respectively]. Multi-organ injury may be presented in acute stroke patients with high blood pressure. Patients with high blood pressure had a poor functional outcome after acute ischemic stroke.

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