scholarly journals Increased Serum and Urinary MicroRNAs in Children with Idiopathic Nephrotic Syndrome

2013 ◽  
Vol 59 (4) ◽  
pp. 658-666 ◽  
Author(s):  
Yang Luo ◽  
Cheng Wang ◽  
Xi Chen ◽  
Tianying Zhong ◽  
Xiaoyi Cai ◽  
...  

BACKGROUND MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86–0.94; P < 0.0001) and 40.7 (95% CI, 6.06–103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.

2021 ◽  
Author(s):  
Robert Sinto ◽  
Dwi Utomo ◽  
Suwarti Suwarti ◽  
Erni J Nelwan ◽  
Henry Surendra ◽  
...  

Background: The inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. Methods: In a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (median 190 days, IQR165-232), we measured anti-Spike IgG titers on paired serum samples taken before and 28 days after a 100μg mRNA-1273 (Moderna) booster. We performed correlations and multivariable ordinal regressions. Findings: Among 304 participants, the median age was 31 years (range 21-59), 235 (77.3%) were women, 197 (64.8%) had one or more previous SARS-CoV-2 infections (including 155 [51.0%] who had a post-CoronaVac breakthrough infection. Pre-boost IgG titers correlated negatively with the time since the latest documented virus exposure (either by the second CoronaVac or SARS-CoV-2-infection whichever most recent). Previous SARS-CoV-2 infection and a longer time interval between second vaccine and mRNA-1273 boost were associated with a higher pre-boost IgG titer. Post-booster, the median IgG titer increased 9.3-fold, from 250 (IQR32-1389) to 2313 (IQR1226-4324) binding antibody units (BAU/mL) (p<0.001). All participants, including seven whose pre-boost IgG was below assay detection limits, became seropositive and all reached a substantial post-boost titer (≥364 BAU/mL). Post-boost IgG was not associated with pre-boost titer or previous SARS-CoV-2 infection. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living (ADL). Interpretation: A heterologous, high-dose mRNA-1273 booster after two-dose CoronaVac was highly immunogenic and safe, including in those most in need of improved immunity. Funding: Wellcome Trust, UK Keywords SARS-CoV-2; COVID-19; inactivated vaccine; CoronaVac; mRNA-1273; antibodies


2007 ◽  
Vol 53 (2) ◽  
pp. 241-250 ◽  
Author(s):  
William CS Cho ◽  
Timothy TC Yip ◽  
Roger KC Ngan ◽  
Tai-Tung Yip ◽  
Vladimir N Podust ◽  
...  

Abstract Background: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. Methods: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. Results: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interα-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. Conclusions: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.


Author(s):  
Nishanth Parameswaran ◽  
Oriol Mitjà ◽  
Christian Bottomley ◽  
Cynthia Kwakye ◽  
Wendy Houinei ◽  
...  

WHO and its partners aim to interrupt yaws transmission in endemic countries and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6–15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semi-quantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold-change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.


2021 ◽  
Author(s):  
Łukasz Pietrzyk ◽  
Kamil Torres

Abstract Background: Colorectal cancer (CRC) is an important global burden, and the discovery of biomarkers for screening and monitoring is a current challenge. The present study aimed to determine the serum concentration of ROBO4 and CLEC14A in CRC patients and assess the clinical value of these diagnostic and progression biomarkers in CRC.Methods: Serum samples were collected from 32 patients with operable colorectal cancer and from 16 healthy individuals. Blood serum of CRC patients were tested at two time points (before and after surgery). Serum concentration of ROBO4 and CLEC14A were measured using ELISA tests.Results: The serum concentrations of ROBO4 and CLEC14A were significantly higher in CRC patients than non-cancer controls; the concentrations were already higher in TNM stage I + II CRC patients. The sensitivitiy and specificity of ROBO4 and CLEC14A in distiguishing cancer patients form controls ranged from 71.9–100% and from 84.5–100%, respectively. The serum ROBO4 concentration was associated with the TNM stage, depth of invasion, and lymph node and distant metastases. No significant relationship was observed between the CLEC14A concentration and the tumor site or the N and M stages. The level of ROBO4 was statistically lower 3 months after the surgery, compared to the level noted prior to the operation. The concentration of CLEC14A decreased in the postoperative period, compared to preoperative one; however, the decline was not statistically significant.Conclusion: Our preliminary study has provided evidence that ROOB4 and CLEC14A seem to be suitable biomarkers for clinical diagnostic purposes. However, ROOB4 appears to be more appropriate for assessment of CRC progression.


2020 ◽  
Author(s):  
Amanda P. Waller ◽  
Shipra Agrawal ◽  
Katelyn J. Wolfgang ◽  
Jiro Kino ◽  
Melinda A. Chanley ◽  
...  

ABSTRACTBackgroundThrombosis is a potentially life-threatening nephrotic syndrome (NS) complication. We have previously demonstrated that hypercoagulopathy is proportional to NS severity in rat models and that pioglitazone (Pio) reduces proteinuria both independently and in combination with methylprednisolone (MP), a glucocorticoid (GC). However, the effect of these treatments on NS-associated hypercoagulopathy remains unknown. We thus sought to determine the ability of Pio and GC to alleviate NS-associated hypercoagulopathy.MethodsPuromycin aminonucleoside-induced rat NS was treated with sham, Low- or High-dose MP, Pio, or combination (Pio+Low-MP) and plasma was collected at day 11. Plasma samples were collected from children with steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) upon presentation and after 7 weeks of GC therapy. Plasma endogenous thrombin potential (ETP), antithrombin (AT) activity, and albumin (Alb) were measured using thrombin generation, amidolytic, and colorimetric assays, respectively.ResultsIn a rat model of NS, both High-MP and Pio improved proteinuria and corrected hypoalbuminemia, ETP and AT activity (P<0.05). Proteinuria (P=0.005) and hypoalbuminemia (P<0.001) were correlated with ETP. In childhood NS, while ETP was not different at presentation, GC therapy improved proteinuria, hypoalbuminemia, and ETP in children with SSNS (P<0.001) but not SRNS (P=0.330).ConclusionsBoth Pio and GC diminish proteinuria and significantly alleviate hypercoagulopathy. Both Pio and MP improved hypercoagulopathy in rats, and successful GC therapy (SSNS) also improved hypercoagulopathy in childhood NS. These data suggest that even a partial reduction in proteinuria may reduce NS-associated thrombotic risk.SIGNIFICANCE STATEMENTNephrotic syndrome (NS) is characterized by massive proteinuria and is complicated by a complex, acquired hypercoagulopathy that markedly increases the risk for potentially life-threatening venous thromboembolism (VTE). This study demonstrates a strong correlation between proteinuria reduction and improvement of an established VTE-risk biomarker, in both a well-established animal model and in childhood NS before and after steroid treatment. We show that nuclear receptor agonists with known disparate mechanisms of action successfully reduce proteinuria and simultaneously improve NS-associated hypercoagulopathy. These data suggest that complete or partial proteinuria reduction by any therapeutic modality may concurrently reduce NS-associated thrombotic risk.


2010 ◽  
Vol 56 (12) ◽  
pp. 1871-1879 ◽  
Author(s):  
Chunni Zhang ◽  
Cheng Wang ◽  
Xi Chen ◽  
Cuihua Yang ◽  
Ke Li ◽  
...  

BACKGROUND Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker. METHODS Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe–based stem–loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls. RESULTS The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P &lt; 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls. CONCLUSIONS This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.


2007 ◽  
Vol 53 (10) ◽  
pp. 1860-1863 ◽  
Author(s):  
Manuel Collado ◽  
Vanesa Garcia ◽  
Jose Miguel Garcia ◽  
Isabel Alonso ◽  
Luis Lombardia ◽  
...  

Abstract Background: The blood of cancer patients is known to contain fragments of RNA released from the tumor. The application of genomic profiling techniques to plasma RNA may allow the unbiased selection of cancer markers in the blood, but the informative value of genomic profiling of plasma RNA is currently unknown. Methods: We used cDNA microarray hybridization to perform genomic profiling of plasma RNA from colorectal cancer (CRC) patients and from healthy donors. From a list of 40 genes differentially upregulated in cancer patients, we randomly selected 4 genes for further characterization. These 4 markers were analyzed by quantitative reverse-transcription PCR in a wide set of samples including paired samples from the same CRC patients before and after surgical resection of the tumor. Results: Three of the selected markers—EPAS1, UBE2D3, and KIAA0101—were confirmed by PCR to be significantly increased in cancer compared to healthy donors. Importantly, 2 of the markers, EPAS1 and UBE2D3, showed a significant decrease after surgery, returning to the levels of healthy donors. Finally, supervised class prediction using these 3 markers correctly (77%) assigned presurgery samples to the CRC group and assigned postsurgery samples from the same patients to the healthy group. Conclusions: Our findings demonstrate the usefulness of gene expression profiling of circulating plasma RNA to find cancer markers of potential clinical value.


Author(s):  
Sara Pasqualetti ◽  
Dominika Szőke ◽  
Mauro Panteghini

AbstractBackground:Pneumatic tube transportation (PTT) may induce hemolysis (H) in blood samples. We aimed to compare the H degree before and after PTT implementation in our hospital.Methods:Hemolysis indices (HI) for all lithium-heparin plasma samples (P) drawn by the Emergency Department in 2-month periods were retrospectively collected and pre- (n=3579) and post-PTT (n=3469) results compared. The impact of PTT introduction was investigated on LDH [HI threshold (HIt), 25], conjugated bilirubin (cBIL) (HIt, 30), K (HIt, 100) and ALT (HIt, 125). In addition, HI retrieved for P and paired serum samples collected in silica clot activator tubes (S) from the same venipuncture were compared in pre- (n=501) and post-PTT (n=509) periods.Results:Median (5–95th percentile) HI in P was significantly higher in post-PTT period [7 (0–112) vs. 6 (0–82), p<0.001]. Results reported as ‘Hemolysis’ in P increased from 6.6% in pre-PTT to 9.4% in post-PTT (p<0.001). Investigated tests gave the following rejection rates (pre-PTT vs. post-PTT): LDH, 13.4% vs. 18.8%, p<0.001; cBIL, 9.4% vs. 27.0%, p<0.05; K, 3.7% vs. 5.6%, p<0.001; ALT, 2.9% vs. 4.4%, p<0.01. The slightly higher susceptibility to H of S compared to paired P found in the pre-PTT [9 (1–64) vs. 6 (0–85)] was not confirmed in the post-PTT period [7 (0–90) vs. 8 (1–72)], in which median HI in S was significantly lower (p<0.001) than in pre-PTT.Conclusions:In our setting PTT promotes H in P, increasing the rate of rejected tests. The use of S appears to protect against the hemolysing effect of PTT.


Author(s):  
Seri Jeong ◽  
Nuri Lee ◽  
Su Kyung Lee ◽  
Eun-Jung Cho ◽  
Jungwon Hyun ◽  
...  

Reliable results of serologic positivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential to estimate the efficacy of vaccination. We assessed the positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11-28 days after the first dose of AZ. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on symptom, severity, and duration of adverse reactions was completed by all participants. The overall positive rates for SARS-CoV-2 antibody were 84.6% for Roche, 92.5% for Abbott, 75.4% for Siemens, 90.7% for SD Biosensor, and 66.2% for GenScript assays after the first dose of AZ vaccination. The positive rates and antibody titer of sera obtained between 21-28 days were significantly higher than those obtained between 11-20 days in all five assays. More severe and longer duration of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the applied assays were substantial (к=0.73-0.95) and strong (ρ=0.83-0.91). A single dose of AZ vaccination led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversions. The results should be interpreted cautiously considering the applied assays and cutoffs. Our findings could inform decisions regarding vaccination and laboratory settings and, thus, contribute to the control of the spread of SARS-CoV-2 infection.


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