scholarly journals Circulating miRNAs as Potential Biomarkers for Celiac Disease Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Ineke L. Tan ◽  
Rodrigo Coutinho de Almeida ◽  
Rutger Modderman ◽  
Anna Stachurska ◽  
Jackie Dekens ◽  
...  
Keyword(s):  
Celiac Disease ◽  
European Population ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Short Rnas ◽  
Individual Mirnas ◽  
Mirna Sequencing ◽  
Diagnostic Biopsy ◽  
Transcriptional Gene Regulation ◽  
Meta Analyses

Background & AimsCeliac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD.MethodsUsing next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort.Results53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine.ConclusionsWe identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

scholarly journals Circulating microRNAs in Fabry Disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ke Xiao ◽  
Dongchao Lu ◽  
Jeannine Hoepfner ◽  
Laura Santer ◽  
Shashi Gupta ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Premature Death ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Significant Differential Expression ◽  
Enzyme Replacement ◽  
Beneficial Effects ◽  
Mirna Sequencing ◽  
Continuous Progress ◽  
Alpha Galactosidase

Abstract Fabry disease is an X-linked deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal). This results in an accumulation of globotriaosylceramide (GL-3/Gb3) in a variety of cells with subsequent functional impairment. The continuous progress of FD often leads to decreased quality of life and premature death caused by multi-organic complications. The overall aim of our study was to determine the amount of circulating miRNAs in Fabry patients and to test whether ERT would alter the level of individual circulating miRNAs. We used miRNA sequencing by the HTG EdgeSeq System to identify the circulating miRNA pool from Fabry patients with and without enzyme replacement therapy (n = 6). In total, 296 miRNAs in serum of patients were identified. Among them 9 miRNAs were further evaluated in extra serum samples (n = 31) using real-time qPCR and 6 of them showed significant differential expression. The resulting miRNA pattern may help to better understand mechanisms involved in the beneficial effects of ERT and these new miRNA markers could help to estimate the efficacy of ERT or to identify Fabry patients with specific need for ERT.

scholarly journals Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Heyong-Seok Kim ◽  
Ga-Won Lee ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Heart Diseases ◽  
Ductus Arteriosus ◽  
Canine Heart ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Circulating Micrornas ◽  
Concentric Hypertrophy ◽  
Novel Biomarkers ◽  
Healthy Dogs

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

scholarly journals Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2184 ◽  
Author(s):  
Iwona Sidorkiewicz ◽  
Magdalena Niemira ◽  
Katarzyna Maliszewska ◽  
Anna Erol ◽  
Agnieszka Bielska ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Mirna Target ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Roc Curve Analysis

Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

scholarly journals Tools Used to Measure the Physical State of Women with Celiac Disease: A Review with a Systematic Approach

2020 ◽  
Vol 17 (2) ◽  
pp. 539
Author(s):  
Alejandro Martínez-Rodríguez ◽  
Daniela Alejandra Loaiza-Martínez ◽  
Javier Sánchez-Sánchez ◽  
Pablo J. Marcos-Pardo ◽  
Soledad Prats ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Selection Process ◽  
Immunoglobulin A ◽  
Clinical History ◽  
Diagnostic Tools ◽  
Intestinal Biopsy ◽  
Specific Protocol ◽  
Small Intestinal Biopsy ◽  
Immunological Disorder ◽  
Meta Analyses

Celiac disease (CD) is an immunological disorder that mainly affects the small intestine, generating an inflammatory process in response to the presence of gluten (a protein). Autoimmune diseases are part of a group of diseases that are difficult to diagnose without a specific protocol or consensus to detect them due to the number of symptoms and diseases with which it has a relationship. Therefore, the aim of this review was to analyze the diagnostic tools of CD used in middle-aged women, to compare the use and effectiveness of the different tools, and to propose a strategy for the use of the tools based on the results found in the literature. The present research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search was conducted in the following databases: Scielo, PubMed, Web of Science, and Worldwide Science org. In the initial literature search, 2004 titles and relevant abstracts were found. Among them, 687 were duplicates, leaving 1130 articles. Based on the inclusion criteria, only 41 articles passed the selection process; 4 main types of analyses appear in the studies: blood tests, questionnaires, clinical history, and biopsy. It can be said that none of the analyses have a 100% reliability since most of them can present false negatives; therefore, the best way to diagnose celiac disease up to now is through a combination of different tests (Immunoglobulin A and small intestinal biopsy).

scholarly journals Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2810
Author(s):  
Muhammad Yogi Pratama ◽  
Alessia Visintin ◽  
Lory Saveria Crocè ◽  
Claudio Tiribelli ◽  
Devis Pascut
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Therapy Response ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Free Survival ◽  
Microarray Profiling ◽  
Disease Free ◽  
Arterial Chemoembolization

The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD. The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

scholarly journals Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2736
Author(s):  
Venla Ylönen ◽  
Katri Lindfors ◽  
Marleena Repo ◽  
Heini Huhtala ◽  
Valma Fuchs ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Transglutaminase 2 ◽  
Clinical Suspicion ◽  
Family Risk ◽  
Serum Samples ◽  
Clinical Cohort ◽  
The Family ◽  
Endomysial Antibodies ◽  
Commercial Kits ◽  
Diagnostic Investigations

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×–5.1× in the clinical cohort and 1.3×–4.9× in the family cohort, respectively. Using the assays’ own cut-offs (1×ULN) the PPVs ranged 84–100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.

scholarly journals New Automated Immunoassay Measuring Immunoglobulin A Antigliadin Antibodies for Prediction of Celiac Disease in Childhood

2001 ◽  
Vol 8 (3) ◽  
pp. 564-570 ◽  
Author(s):  
E. Grodzinsky ◽  
A. Ivarsson ◽  
P. Juto ◽  
P. Olcén ◽  
K. Fälth-Magnusson ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Characteristic Curve ◽  
Immunoglobulin A ◽  
Total Serum ◽  
Small Intestinal Mucosa ◽  
Serum Samples ◽  
Serological Tests ◽  
Population Prevalence ◽  
Serum Iga ◽  
Antigliadin Antibodies

ABSTRACT The prevalence of celiac disease (CD) in Sweden is about 4 cases per 1,000 people. Screening for CD with serological tests indicates similar high prevalences in many other countries. Between 1 November 1992 and 30 April 1995, 133 children (9 months to 16.7 years of age) with suspected CD were studied. The predictive value (PV) of immunoglobulin A antigliadin antibodies (IgA-AGA) in the serum as assayed with two new commercial automated immunoassays—the Pharmacia CAP System Gliadin IgA FEIA (CAP) and the UNICAP-100 (UNICAP)—and with three “in-house” methods was evaluated using assessment of the small intestinal mucosa morphology as the “gold standard.” All serum samples were analyzed for total serum IgA. At presentation the diagnostic sensitivities and specificities of the different tests varied from 0.72 to 0.88 and 0.67 to 0.87, respectively. All methods showed a higher sensitivity for CD in younger children. The area under each assay's receiver operating characteristic curve was calculated and varied between 0.82 and 0.89. The positive and negative PVs for the CAP and UNICAP, which were assays with a high sensitivity and a high specificity, respectively, were estimated. In the clinically selected population (prevalence of CD, 1 in 3) the positive PV was about 55%, and in the general population (prevalence, 1 in 250) it was about 1%. The negative PVs for both CAP and UNICAP were close to 100%; thus, when the AGA test was negative, the risk for CD was small. Interestingly, five children had serum IgA levels below the detection limit (<0.07 g/liter) when on a gluten-free diet, whereas they had normal levels at the time of the first biopsy. In conclusion, the automated immunoassays—based on ImmunoCAP technology—for analysis of IgA-AGA had a reliability comparable to that of the in-house methods.

Pediatric celiac disease—is a diagnostic biopsy necessary?

2012 ◽  
Vol 9 (3) ◽  
pp. 127-128 ◽  
Author(s):  
Lotta Högberg ◽  
Lars Stenhammar
Keyword(s):  
Celiac Disease ◽  
Diagnostic Biopsy

scholarly journals The Prevalence of Occult Celiac Disease among Patients with Functional Dyspepsia: A Study from the Western Region of Iran

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Ali Asghar Keshavarz ◽  
Homayoon Bashiri ◽  
Alireza Ahmadi ◽  
Shahrzad Bazargan-Hejazi
Keyword(s):  
Celiac Disease ◽  
Functional Dyspepsia ◽  
Western Region ◽  
Cross Sectional ◽  
Diagnostic Biopsy ◽  
History Of ◽  
The Western Region ◽  
Upper Abdominal ◽  
Recruitment Period

Objective. The prevalence of Celiac Disease (CD) is high in Iran, and evaluation of CD is not part of the routine screening procedure for dyspeptic patients; therefore, cases of occult CD may be missed. This study aimed to investigate the prevalence of occult CD among dyspeptic patients who presented at a gastroenterology clinic in the Western region of Iran.Methods. In this descriptive, cross-sectional prospective study, patients who had a history of at least 12 weeks of upper abdominal discomfort were eligible to participate in the study during a 14-month recruitment period. Patients with a clinical or paraclinical data in favor of organic causes were excluded from the study. Enrolled patients were screened for IgA antiendomysium antibody (EMA) and IgA antitissue transglutaminase antibody (tTG). Those who screened positive for EMA/tTG received a confirmatory diagnostic biopsy for Marsh classification of CD.Results. From 225 potential participants with dyspepsia, 55 patients were excluded due to having explainable organic causes. The study sample included 170 patients with “functional dyspepsia.” Mean age of participants was 31 years and 55.8% were female. Twelve patients (7%) had positive tests (EMA/tTG), of which 10 were female (83.4%). According to Rome II criteria, all twelve patients with positive tests had “dysmotility type dyspepsia.” Based on Marsh classification, six patients were consistent with “Marsh I,” four with “Marsh II,” and two with the “Marsh III” classification.Conclusions. In this study, the prevalence of CD in dyspeptic patients was high. As a result, this study suggests that screening by serology tests (EMA/tTG) is justifiable for the detection of CD among functional dyspeptic patients in the tertiary centers in our country.

Circulating Mir-130a in Multiple Myeloma and Extramedullary Myeloma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2043-2043 ◽  
Author(s):  
Lenka Kubiczkova-Besse ◽  
Lenka Sedlarikova ◽  
Fedor Kryukov ◽  
Lenka Radova ◽  
Jana Nekvindova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Area Under The Curve ◽  
Newly Diagnosed ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Reactive Protein ◽  
Specificity And Sensitivity ◽  
Healthy Donors ◽  
Wide Range

Abstract Background MicroRNAs (miRNAs) are a class of short, non-coding, single stranded RNAs regulating a broad spectrum of processes. Circulating miRNAs are an important emerging biomarker in cancer as well as a possible non-invasive diagnostic solution for a wide range of clinical disorders due to their high stability and association with disease state, although their source still remains uncertain. In multiple myeloma (MM), a plasma cell malignancy, circulating miRNAs have been reported to have a diagnostic and prognostic potential. It is therefore plausible to assume that they are involved in pathogenesis of this disease and thus could be used as diagnostic tool not only for MM, its extramedullary (EM) form but also for monitoring the clinical course of the disease. Therefore, in this study, we aimed to identify such miRNAs. Methods Screening analysis of 667 miRNAs was performed on 5 EM serum samples, 5 newly diagnosed MM samples and 6 healthy donors (HD) serum samples using TaqMan Low Density Arrays (TLDA) from Life Technologies. QPCR was performed for miR-130a on 118 serum samples obtained in Brno from newly diagnosed MM patients (pts) (35 pts), primary and secondary EM (35 pts), relapsed MM (18 pts) and HD (30). Further, 45 serum samples (12 diagnostic and 33 follow-up) of pts reaching VGPR/better response, enrolled in Italian CRD/MEL-200 and EMN-02 studies were used for circulating miRNA estimation. Receiver Operating Characteristic (ROC) analysis was used to calculate specificity and sensitivity of the miRNA as a biomarker. Biochemical characteristics were also available for EM and MM pts from Brno. P values <0.05 were considered as significant. Results TLDA profiling revealed 14 deregulated miRNAs (all p<0.05, adjusted p<0.41) between MM pts and EM pts, and 20 miRNAs were on the top of the list of deregulated miRNAs between EM and HD serum samples (all p<0.05, adjusted p<0.40). MiR-130a was chosen for further verification by qPCR as it was on the top of the list of deregulated miRNAs between the groups. qPCR revealed that level of miR-130a was significantly decreased in MM and EM samples when compared with HD (all p<0.005); moreover, level of miR-130a was decreased also in EM when compared with MM sera (p<0.06). To discriminate EM pts from other groups, ROC curve was calculated. It revealed that miR-130a is potent to distinguish EM pts from HD with area under the curve (AUC) = 0.805, specificity of 86.7% and sensitivity of 65.7% using cut-off value = 3377 copies/1ng of miRNA/RNA. Most importantly, miR-130a was able to distinguish EM pts from newly diagnosed MM pts with AUC = 0.628, specificity of 94.3% and sensitivity of 28.6% using cut-off value = 1438 copies/1ng of miRNA/RNA, and EM pts from MM pts in relapse with AUC = 0.702, specificity of 94.4% and sensitivity of 28.6% using cut-off value = 1438 copies/1ng of miRNA/RNA. In the cohort of EM pts, miR-130a significantly correlated with most of clinically relevant parameters; there was a positive correlation with level of hemoglobin and thrombocytes count (rs=0.397 and 0.439, all p<0.05) and a negative correlation with levels of monoclonal immunoglobulin, β2-microglobulin and C-reactive protein (rs=-0.398, -0.427 and -0.488, all p<0.05) and it was also associated with higher ISS stage (p=0.017). Further, in the analysis of miR-130a dynamics in follow-up samples from Italy, we observed increase of miR-130a levels in 8/12 MM pts during the follow-up sampling (p<0.06) in comparison with diagnostic samples, whereas in remaining 4 MM pts it remained stable or decreased. Conclusions In this study, miR-130a was decreased in serum samples of pts developing EM disease and distinguished EM pts from newly diagnosed MM pts and relapsed/progressed MM pts with specificity over 90%. Further, we observed increased level of miR-130a in the follow-up samples of MM pts. It suggests that miR-130a could be associated with EM disease; however, underlying biology and origin of miR-130a still remains to be explored. Work was supported by grants IGA NT 12130, NT 14575 and NT 13190. Disclosures Palumbo: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Array BioPharma: Honoraria; Genmab A/S: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Sanofi Aventis: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document