Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD.

ABSTRACT: Introduction:We examined the impact of autoantibodies on the erythropoietin receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD). Methods:A total of 112 Japanese patients with type 2 diabetes who had CKD were enrolled in this study and followed for a mean of 45 months. Sera from these patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent assays. Results:Anti-EPOR antibodies were detected in 26 patients (23%). Anti-EPOR antibodies were associated with low hemoglobin concentrations and decreased renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR antibodies were associated with increased levels of interstitial inflammation. A decrease in renal function was observed more frequently in patients with antibodies than in those without antibodies, and the presence of the antibodies together with well-known clinical parameters, including proteinuria and low glomerular filtration rate, was a significant risk factor for end-stage renal disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti-EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1 mRNA under a high concentration of glucose. Conclusion:Anti-EPOR antibodies might be involved in the progression of renal lesions and in the impaired erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of anti-EPOR antibodies may be an additional predictor for end-stage renal disease in type 2 diabetes.

SUBMITTER: Hara A

PROVIDER: S-EPMC5762966 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients With Type 2 Diabetes and CKD: A <i>Post Hoc</i> Analysis of CREDENCE Trial.

Project description:IntroductionAutoantibodies to erythropoietin receptor (anti-EPOR antibodies) have been identified in patients with various kidney diseases. However, data in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) is limited. We assessed the prevalence of anti-EPOR antibodies and their association with clinical outcomes in this population.MethodsThe CREDENCE randomized patients with T2D and CKD to canagliflozin or placebo. Serum anti-EPOR antibodies, the exposure of interest, were measured using enzyme-linked immunosorbent assay. The primary outcome was doubling of serum creatinine, end-stage kidney disease, or death from kidney or cardiovascular (CV) causes. Secondary outcomes included CV and all-cause mortality. Multivariable Cox-regression models estimated associations between anti-EPOR antibodies and outcomes. The effects of canagliflozin on hemoglobin and hematocrit, stratified by the presence of anti-EPOR antibodies were assessed with a repeated measures mixed effects model.ResultsOf 2600 participants with available biosamples, 191 (7.3%) were positive for anti-EPOR antibodies. Higher baseline anti-EPOR antibodies were associated with increased risk of primary outcome (hazard ratio [HR] per 1-SD increase = 1.12, 95% confidence interval [CI] = 1.01-1.24, P = 0.04), with CV death (HR = 1.27, 95% CI = 1.08-1.48, P < 0.01) and all-cause mortality (HR = 1.26, 95% CI = 1.11-1.43, P < 0.01). During follow-up, canagliflozin, compared to placebo, increased hemoglobin and hematocrit by 7.0 g/l (95% CI = 6.2-7.9) and 2.4% (2.2-2.7), respectively. These effects were consistent across patients with and without anti-EPOR antibodies (P-interaction = 0.24 and 0.36, respectively).ConclusionIn patients with T2D and CKD, anti-EPOR antibodies were associated with the composite kidney and CV outcome, as well as CV and all-cause mortality. Canagliflozin increased hemoglobin and hematocrit regardless of anti-EPOR antibodies.

| S-EPMC10850998 | biostudies-literature

Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor.

Project description:IntroductionSeveral circulating markers, including autoantibodies to erythropoietin receptor (anti-EPOR antibodies), have been identified as useful biomarkers in predicting diabetic kidney disease progression. However, a direct comparison of their utility is lacking. We aimed to validate and to compare the prognostic value of anti-EPOR antibodies with that of other known biomarkers, using the ADVANCE trial and its long-term follow-up, ADVANCE-ON, cohorts.MethodsIn this nested case-control study from the ADVANCE trial cohort, we included 165 case participants who had the composite kidney outcome (renal replacement therapy, renal death, or doubling of serum creatinine to ≥200 μmol/l) and 330 matched controls. We compared the associations of baseline plasma levels of anti-EPOR antibodies, tumor necrosis factor receptor (TNFR)-1 and -2, and bone morphogenetic protein (BMP)-7 with kidney outcomes.ResultsCases had higher baseline plasma levels of anti-EPOR antibodies than controls (median 1.7 vs. 0.6 enzyme-linked immunosorbent assay unit, P < 0.001). Higher levels of anti-EPOR antibodies were associated with an increased risk of kidney outcome (odds ratio 2.16 [95% confidence interval 1.51, 3.08], per 1 SD of log-transformed levels) after adjusting for conventional markers. Elevated circulating TNFR1 and TNFR2 levels, and lower BMP-7 levels at baseline, were associated with poor kidney outcome (odds ratios 2.06 [1.29, 3.30], 1.66 [1.13, 2.43], and 0.45 [0.32, 0.65], respectively). The addition of anti-EPOR antibodies into the model improved the prediction of kidney outcome, regardless of other biomarkers.ConclusionAnti-EPOR antibodies provide a promising biomarker, as with TNFR1, TNFR2, and BMP-7, in predicting kidney disease progression in people with type 2 diabetes mellitus.

| S-EPMC7879109 | biostudies-literature

Clinical usefulness of anti-muscarinic type 3 receptor autoantibodies in patients with primary Sjogren's syndrome.

Project description:ObjectivesTo elucidate the clinical values of anti-M3R in Sjögren's syndrome (SS) in the largest cohort for an anti-M3R study.MethodsThe plasma of 361 subjects (156 primary SS [pSS], 62 non-SS-sicca [SICCA], 40 systemic lupus erythematosus [SLE], 50 rheumatoid arthritis [RA], and 53 healthy controls [HC]) was screened using our modified On-Cell-Western assay. Saliva from pSS (n=37) compared to SICCA (n=26) was also analysed. The sensitivity and specificity of anti-M3R and its association with comprehensive clinical and laboratory features were determined.ResultsPlasma-anti-M3R was higher in pSS compared to other groups, differentiating pSS with good-to-excellent diagnostic power with a specificity of 85% and a sensitivity between 75% and 98%. pSS plasma-anti-M3R was positively correlated with ocular staining scores, anti-Ro/SSA, IgG, β2-microglobulin, ESR, and ESSDAI. It was negatively correlated with WBC, C4, and salivary scintigraphic indices. Saliva-anti-M3R was 3.59 times higher in pSS than in SICCA. Interestingly, the agreement between the 2002 American European Consensus Group criteria and the criteria substituted with plasma-anti-M3R for the lip biopsy reached 92%, with a significant kappa of 0.824.ConclusionsAnti-M3R enhances sensitivity and specificity for SS diagnosis, correlating with ocular dryness and glandular hypofunction, and the haematological/biological domains of the ESSDAI. Our findings also highlight the clinical significance of anti-M3R in SS diagnosis, especially where clinical assessments, such as lip biopsy, sialometry, or ocular evaluation, by multi-disciplinary specialists are limited.

| S-EPMC8021605 | biostudies-literature

Targeting erythropoietin protects against proteinuria in type 2 diabetic patients and in zebrafish.

Project description:OBJECTIVE:Adult human kidneys produce erythropoietin (EPO), which regulates red blood cell formation; however, whether EPO also functions directly on kidney development and controls diabetic kidney disease remains unknown. Here we analyzed the role of EPO in kidney development and under hyperglycemic conditions in zebrafish and in humans. METHODS:Diabetic patients and respective controls were enrolled in two cohorts. Serum EPO level and urine protein change upon human EPO administration were then analyzed. Transient knockdown and permanent knockout of EPO and EPOR in renal TG(WT1B:EGFP) zebrafish were established using the morpholino technology and CRISPR/Cas9 technology. Zebrafish embryos were phenotypically analyzed using fluorescence microscopy, and functional assays were carried out with the help of TexasRed labeled 70 kDa Dextran. Apoptosis was determined using the TUNEL assay and Annexin V staining, and caspase inhibitor zVADfmk was used for rescue experiments. RESULTS:In type 2 diabetic patients, serum EPO level decreased with the duration of diabetes, which was linked to reduced kidney function. Human recombinant EPO supplementation ameliorated proteinuria in diabetic nephropathy patients. In zebrafish, loss-of-function studies for EPO and EPOR, showed morphological and functional alterations within the pronephros, adversely affecting pronephric structure, leading to slit diaphragm dysfunction by increasing apoptosis within the pronephros. Induction of hyperglycemia in zebrafish embryos induced pronephros alterations which were further worsened upon silencing of EPO expression. CONCLUSIONS:EPO was identified as a direct renal protective factor, promoting renal embryonic development and protecting kidneys from hyperglycemia induced nephropathy.

| S-EPMC5985015 | biostudies-literature

Clinical and Pathological Characteristics of Patients With Nonproteinuric Diabetic Nephropathy.

Project description:IntroductionAs the most common complication of diabetes mellitus (DM), diabetic nephropathy (DN) was initially considered to begin with proteinuria preceding the progression of renal insufficiency. This clinical paradigm has been questioned in the late decades, as many DM patients without proteinuria have progressive renal insufficiency. However, the characteristics of nonproteinuric DN were not fully clear yet.Patients and methodsA total of 390 patients with renal biopsy-proven DN in our center were retrospectively recruited in the current study. Clinical and histopathological data of the patients were analyzed. We used propensity score-matching methods to address the imbalance of age, sex, and diabetes duration for comparative analyses.ResultsAmong all the renal biopsy-proven DN patients with renal biopsy proven DN, 18 patients were classified as nonproteinuric DN. Compared with 36 propensity score-matched proteinuric DN patients, diabetic retinopathy (DR) was less frequent in nonproteinuric DN patients (38.9% vs. 66.4%, p<0.05). During the follow-up of 24.0 (12.0-42.0) months, the probability of developing the end-stage renal disease (ESRD) was significantly lower in nonproteinuric DN patients than in proteinuric ones in both the propensity score-matched cohort and overall cohort (log-rank test, p<0.001 and p<0.001, respectively).ConclusionsCompared with proteinuric DN patients, DR was less frequent in nonproteinuric DN patients. Nonproteinuric DN patients had better renal outcomes than proteinuric DN patients.

| S-EPMC8576342 | biostudies-literature

VEGFA activates erythropoietin receptor and enhances VEGFR2-mediated pathological angiogenesis.

Project description:Clinical and animal studies implicate erythropoietin (EPO) and EPO receptor (EPOR) signaling in angiogenesis. In the eye, EPO is involved in both physiological and pathological angiogenesis in the retina. We hypothesized that EPOR signaling is important in pathological angiogenesis and tested this hypothesis using a rat model of oxygen-induced retinopathy that is representative of human retinopathy of prematurity. We first determined that EPOR expression and activation were increased and that activated EPOR was localized to retinal vascular endothelial cells (ECs) in retinas at postnatal day 18 (p18), when pathological angiogenesis in the form of intravitreal neovascularization occurred. In human retinal microvascular ECs, EPOR was up-regulated and activated by VEGF. Lentiviral-delivered shRNAs that knocked down Müller cell-expressed VEGF in the retinopathy of prematurity model also reduced phosphorylated EPOR (p-EPOR) and VEGFR2 (p-VEGFR2) in retinal ECs. In human retinal microvascular ECs, VEGFR2-activated EPOR caused an interaction between p-EPOR and p-VEGFR2; knockdown of EPOR by siRNA transfection reduced VEGF-induced EC proliferation in association with reduced p-VEGFR2 and p-STAT3; however, inhibition of VEGFR2 activation by siRNA transfection or semaxanib (SU5416) abolished VEGFA-induced proliferation of ECs and phosphorylation of VEGFR2, EPOR, and STAT3. Our results show that VEGFA-induced p-VEGFR2 activates EPOR and causes an interaction between p-EPOR and p-VEGFR2 to enhance VEGFA-induced EC proliferation by exacerbating STAT3 activation, leading to pathological angiogenesis.

| S-EPMC3969997 | biostudies-literature

Clinical significance of serum autoantibodies in idiopathic interstitial pneumonia.

Project description:Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

| S-EPMC3653086 | biostudies-other

Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network.

Project description:PurposeSome studies have suggested that autoantibodies might define a subcategory and phenotype of nonalcoholic fatty liver disease (NAFLD) associated with advanced histological features. We evaluated the relationship between the presence of serum autoantibodies and liver histology in a large cohort of well-characterized patients with NAFLD.MethodsA total of 864 NAFLD patients participating in two prospective multicentre clinical studies underwent testing for serum autoantibodies within 24 months of a liver biopsy. Liver histology was compared between the patients with and without ANA ≥ 1:160 or ASMA ≥ 1:40 or both.ResultsAutoantibodies were present in 182 patients (21%). There was no difference in age, gender, race, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), or history of diabetes between the two groups. Biopsies in subjects with autoantibodies were less likely to have moderate-to-severe steatosis (i.e., >33%) compared to controls (57.1 vs. 43.0%, P value = 0.0006). Lobular inflammation (46.7 vs. 47.5%), ballooning degeneration (38.5 vs. 42.5%), and advanced fibrosis (33.2 vs. 29.3%) were not different between the two groups. Histologic evidence of 'definite' NASH did not differ significantly between the two groups (55.5 vs. 58.9%). After adjusting for age, gender, BMI, race, and diabetes, the presence of autoantibodies was independently associated with lower prevalence of moderate-to-severe steatosis [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.41-0.82; P = 0.01].ConclusionAutoantibodies are frequently positive in NAFLD in the absence of autoimmune hepatitis and their occurrence is not associated with more advanced histologic features.

| S-EPMC3511661 | biostudies-literature

Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI.

Project description:BackgroundMyelin-oligodendrocyte-glycoprotein (MOG)-IgG-positivity in patients with typical MS lesions on MRI may lead to diagnostic/therapeutic uncertainty.Objective and methodsWe reviewed reports of cases with MS phenotype on MRI and MOG-IgG-positivity published in Pubmed between 01/2012-06/2021.ResultsSixteen patients were included (median age [range], 37,5 [25-66] years; 60% female). Three patients initially tested negative for MOG-IgG. Disease course was: relapsing-remitting, 10; or progressive, 6. Intrathecal IgG-synthesis was common (79%). Low and high-efficacy MS-targeted agents prevented relapses in 30% and 100%, respectively. None of the patients showed resolution of MRI T2-lesions over time.ConclusionsMOG-IgG-positivity is unlikely to alter the expected treatment response and outcomes in patients with otherwise typical MS phenotype on MRI.

| S-EPMC8606934 | biostudies-literature

Albuminuria during treatment with angiotensin type II receptor blocker is a predictor for GFR decline among non-diabetic hypertensive CKD patients.

Project description:BACKGROUND:Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear. METHOD:This observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0-4 months, 0-26 months, and 0-38 months. The renal outcome was defined as a decline in eGFR ≥ 40% during the entire study period. RESULT:The albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR ≥ 40% was increased by 1.690-folds [95% CI 1.110-2.572, P = 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR ≥ 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients. CONCLUSION:The time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR ≥ 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome.

| S-EPMC6110474 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data