Urinary Peptides Research Articles

Risk factors and diagnostic value of urinary N-terminal pro-brain natriuretic peptide for verification of heart failure in human immunodeficiency virus-infected patients

Aim. To determine the risk factors and diagnostic value of urinary N-terminal probrain natriuretic peptide (NT-proBNP) for verification of heart failure in human immunodeficiency virus (HIV)-infected patientsMaterial and methods. This cross-sectional screening clinical trial included 115 HIV-infected patients who were hospitalized during 24 months. The patients were divided into 2 groups, depending on the data suggestive of HF and the blood and urinary NT-proBNP concentration. So, group 1 included 69 HIV-infected patients with HF symptoms and increased blood and urinary NTproBNP, while group 2 — 46 HIV-infected patients not meeting HF criteria. NTproBNP concentration was determined on Immulite 1000 Immunoassay System (DPC, USA) in blood plasma and frozen urine using Vector Best reagents (Russia).Results. Correlation analysis revealed a significant direct moderate correlation between blood and urinary NT-proBNP in the entire cohort of studied patients (r=0,367; p<0,05). Urinary NT-proBNP ≥8,6 pg/ml ml is diagnostic for HF verification in HIV-infected patients. Significant differences between the groups were obtained in the incidence of ventricular arrhythmias, viral hepatitis B and C, liver cirrhosis, infective endocarditis, other inflammatory diseases, thrombocytopenia, left ventricular (LV) diastolic dysfunction and its severity. In addition, there were differences in LV mass index, left atrial volume index, incidence of LV hypertrophy and left atrial enlargement, concentration of hemoglobin and CD4 cells <200 in 1 µl. The preserved LV ejection fraction was detected significantly more often (p<0,001). Conclusion. In HIV-infected patients, blood plasma and urinary NT-proBNP concentration correlates with each other. Urinary NT-proBNP ≥8,6 pg/ml is diagnostic for HF verification in HIV-infected patients. Risk factors and features of developing HF, estimated by NT-proBNP concentration in frozen urine in HIV-infected patients, are comparable to data obtained from blood plasma NTproBNP.

Biomarkers for the diagnosis and monitoring of celiac disease: can you count on me?

Different markers are available to diagnose and monitor celiac disease (CeD); however, the concordance among them and their efficacy are still controversial. We aim at defining the efficacy of CeD biomarkers, their advantages and limits. CeD diagnostic criteria are widely accepted, being a positive serology and duodenal atrophy (according to the Marsh-Oberhuber score) the main hallmarks. Flow cytometry and other molecular biomarkers support the diagnosis of refractory CeD. On the other side, CeD monitoring is less defined, as the biomarkers are not always reliable. To date, the reference standard to detect mucosal healing is represented by duodenal histology, but its timing and significance are debated. Novel scores may better define the trend of mucosal damage and MicroRNAs are among the innovative noninvasive biomarkers. The assessment of a correct gluten-free diet (GFD) is another aspect of CeD monitoring, based upon questionnaires and recently developed tools such as dosage of urinary or faecal gluten immunogenic peptides. Clinicians lack of a widely acknowledged tools to monitor CeD and GFD. Here, we present the efficacy of the most used markers.

Maintaining, Managing, and Tele-Monitoring a Nutritionally Adequate Mediterranean Gluten-Free Diet and Proper Lifestyle in Adult Patients

The gluten-free diet (GFD) is a restrictive diet. In many cases, it must be permanent and strict, and it may be associated with both nutritional deficiencies and excesses, which can be prevented by following a healthy, natural Mediterranean GFD (Med-GFD). In this paper, we describe the importance of the Mediterranean diet, the correct intake of vitamins and minerals, and how they may play an important protective role against chronic or degenerative conditions. Herewith, we analyze different aspects that influence the ability to maintain a correct and balanced Med-GFD, which may contribute to the health status of patients, including a conscious use of gluten-free products to maintain a healthy lifestyle. Monitoring the Med-GFD remains a pivotal issue: to evaluate the presence of gluten peptides in urine, it could be important to introduce point-of-care testing, an efficient method for GFD self-monitoring (immunochromatographic technique), together with online nutritional questionnaires. Indeed, medical care via telemedicine can provide practical indications aimed at supporting patients and doctors. A natural Med-GFD can ensure the correct intake of nutrients and could be important for patients affected by gluten-related disorders, helping them to maintain a correct and healthy lifestyle.

Urine peptidome in combination with transcriptomics analysis highlights MMP7, MMP14 and PCSK5 for further investigation in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by the loss of kidney function. The molecular mechanisms underlying the development and progression of CKD are still not fully understood. Among others, the urinary peptidome has been extensively studied, with several urinary peptides effectively detecting disease progression. However, their link to proteolytic events has not been made yet. This study aimed to predict the proteases involved in the generation of CKD-associated urinary excreted peptides in a well-matched (for age, sex, lack of heart disease) case-control study. The urinary peptide profiles from CKD (n = 241) and controls (n = 240) were compared and statistically analyzed. The in-silico analysis of the involved proteases was performed using Proteasix and proteases activity was predicted based on the abundance changes of the associated peptides. Predictions were cross-correlated to transcriptomics datasets by using the Nephroseq database. Information on the respective protease inhibitors was also retrieved from the MEROPS database. Totally, 303 urinary peptides were significantly associated with CKD. Among the most frequently observed were fragments of collagen types I, II and III, uromodulin, albumin and beta-2-microglobulin. Proteasix predicted 16 proteases involved in their generation. Through investigating CKD-associated transcriptomics datasets, several proteases are highlighted including members of matrix metalloproteinases (MMP7, MMP14) and serine proteases (PCSK5); laying the foundation for further studies towards elucidating their role in CKD pathophysiology.

Detection of gluten immunogenic peptides and the Celiac Disease Adherence Test to monitor gluten-free diet: a pilot study.

Gluten immunogenic peptides (GIP) in feces and/or urine have recently been proposed as a sensitive and specific marker to detect ongoing gluten intake. Here, we compared GIP with the Celiac Disease Adherence Test (CDAT), a simple validated self-administered questionnaire that measures adherence to gluten-free diet (GFD). Of 70 subjects (59 women), six were classified as non-adherent by fecal GIP (mean 0.23 µg/g, standard deviation 0.08, range 0.082-0.319), including five classified as non-adherent by CDAT. GFD adherence was significantly higher by GIP than CDAT (p < 0.001). Fecal GIP may be useful as a biomarker for ongoing gluten intake that is not possible to detect with current clinical methods to assess GFD adherence, and may play a role in the management of persistent gastrointestinal symptoms in celiac disease.

Association in Clinical Practice Between Gluten Intake and Gluten Immunogenic Peptides in Celiac Children.

The dietary compliance and its assessment in celiac disease (CD) patients on a strict gluten-free diet (GFD) remain a challenge. Two relatively new, validated methods have been proposed to detect occasional gluten ingestion: standardized dietary questionnaire and determination of urinary gluten immunogenic peptides (GIPs). Our aim was to prospectively assess dietary compliance via these methods and compare their results with those of tissue transglutaminase antibodies (tTGA). This was a prospective single-center study. Consecutive CD patients (aged 1-18 years) on a GFD scheduled for regular consultation between March and August 2019 were invited. In addition to standard care, a completed dietary questionnaire and urine sample for GIP were collected. Pearson's chi-square test, Fisher's exact test, and Mann-Whitney U test were performed. Of the 156 eligible children, 110 provided informed consent. Completed dietary questionnaire, GIP, and tTGA results were available from 86 children (median age 12.8 years, median GFD duration 30 months, 65% female). Adherence to the GFD evaluated by GIP, dietary questionnaire, and anti-tTGA was 94.2%, 75.6% and 94.2%, respectively. No association was found between the tTGA results and the detection of GIP, as well as between the tTGA results and the dietary questionnaires scores (P= .5 and .312, respectively). The participants perceived both the questionnaire and the measurement of GIP as reassuring with regard to correct implementation of the GFD. All the 3 methods have limitations to monitor dietary compliance. The comparison of their performance shows that the best single method is the use of the validated dietary questionnaire, which should therefore be implemented in the regular care for children with CD. The most effective combination of dietary questionnaire and urinary GIP determination should be used in specific clinical situations.

Molecular Mapping of Urinary Complement Peptides in Kidney Diseases.

Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients’ stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.

Urinary N-terminal Pro-Brain Natriuretic Peptide in Newborn Infants with Cardiac and Pulmonary Diseases.

The aim of this study was to assess the feasibility of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) as noninvasive screening tool for congenital heart diseases in full-term neonates with respiratory distress. A prospective cohort study was conducted on 90 full-term infants. Newborn were assigned into three groups: pulmonary, cardiac, and control groups. Urinary NT-proBNP were measured in all studied groups at day 1 (NT-proBNP1) and day 5 (NT-proBNP5). Urinary NT-proBNP1 was higher in cardiac group compared with pulmonary and control groups (488 ± 91, 321 ± 80, and 218 ± 41 ng/L, respectively; p ≤ 0.001). NT-proBNP5 was lower in pulmonary and control group than cardiac group (245 ± 84, 137 ± 39, and 546 ± 284 ng/L, respectively, with p ≤ 0.001). Receiver operating characteristic (ROC) analysis was performed to assess predictive value of NT-proBNP1 in cardiac and pulmonary populations. ROC showed area under curve of 0.97 and cutoff point of ≥386.5 ng/L referring to a cardiac etiology with sensitivity of 93.3%, specificity of 86.7%, negative predictive value of 93%, and positive predictive value of 88%. Urinary NT-proBNP is feasible to be a noninvasive screening tool to predict congenital heart diseases in full-term neonates. Further studies are needed to assess the correlation between plasma and urinary levels of NT-proBNP in congenital heart diseases in full-term and preterm infants.

Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy

BackgroundIdiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases.ResultsPeptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN.ConclusionsThis work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.

Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study.

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.

Urinary Protein and Peptide Markers in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a non-specific type of kidney disease that causes a gradual decline in kidney function (from months to years). CKD is a significant risk factor for death, cardiovascular disease, and end-stage renal disease. CKDs of different origins may have the same clinical and laboratory manifestations but different progression rates, which requires early diagnosis to determine. This review focuses on protein/peptide biomarkers of the leading causes of CKD: diabetic nephropathy, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis, and membranous nephropathy. Mass spectrometry (MS) approaches provided the most information about urinary peptide and protein contents in different nephropathies. New analytical approaches allow urinary proteomic–peptide profiles to be used as early non-invasive diagnostic tools for specific morphological forms of kidney disease and may become a safe alternative to renal biopsy. MS studies of the key pathogenetic mechanisms of renal disease progression may also contribute to developing new approaches for targeted therapy.

Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients

Background: SARS-CoV-2 that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism, and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the Liquid Chromatography Surface-Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry. Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins’ profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed. Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples. Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.

The novel proteomic signature for the detection of cardiac allograft vasculopathy

Abstract Background Cardiac allograft vasculopathy (CAV) is the major long-term complications after heart transplantation, leading to mortality and re-transplantation. As available noninvasive biomarkers are scarce for CAV screening, we aimed to identify a proteomic signature for CAV detection. Methods Urinary proteome was measured by capillary electrophoresis coupled to mass spectrometry in 217 heart transplantation recipients. Participants were further randomly and evenly divided into the derivation cohort and validation cohort. The proteomic signature for CAV was identified by decision tree-based machine learning in the derivation cohort and further tested in the validation cohort. The pathway analysis was investigated with Reactome Pathway Database. Results We identified a proteomic signature with 27 urinary peptides, which yielded areas under the curve (AUC) of 0.83 and 0.71 in the derivation and validation cohort, respectively. In the validation cohort, it had a sensitivity of 68.4%, specificity of 73.2%, accuracy of 71.6%, negative predictive value of 81.3%. Including the proteomic signature into the basic model further improved the diagnostic accuracy with an relative integrated discrimination improvement of 25.9% and the continuous net reclassification improvement of 83.3% (p≤0.023). The pathways analysis on revealed that collagen turnover, platelet aggregation and coagulation, cell adhesion and motility might involve in the pathogenesis of CAV. Conclusions The proteomic signature might be valuable for the surveillance of CAV thereby reduce the frequency of invasive procedures after HTx. Moreover, the highlighted pathways might provide insights in the potential novel treatment targets for CAV. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council Advanced Researcher Grant and Proof-of-Concept Grant ROC curves of the urinary proteomicThe 25 highlighted enrichment pathways

Levels of inter-alpha-trypsin inhibitor heavy chain H4 urinary polypeptide in gestational diabetes mellitus

ABSTRACT Gestational diabetes mellitus (GDM) can cause a variety of adverse maternal and fetal complications. The purpose of this study was to screen and identify the urinary polypeptides related to the severity of GDM and to analyze the correlation between urinary peptide levels and neonatal metabolic indices. A total of 31 normal pregnant women (N group) and 74 patients with GDM (GDM group) were randomly selected between February 2018 and August 2019. Patients with GDM were divided into two groups according to their fasting plasma glucose (FPG) levels. The urine samples were enriched using weak cation-exchange magnetic beads (MB-WCX), and eight different urine polypeptides were screened and analyzed. The peptide spectra were obtained using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The urinary peptide signatures of the two groups were compared using the BioExplorer software. The difference analysis of the eight urinary polypeptides between the normal pregnant (N) group and GDM group showed that two polypeptides with mass-to- charge ratios (m/z) of 2175.7 and 2318.8, respectively, were significantly different between the two groups (P < 0.01). The m/z 2175.7 polypeptide was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS), and the corresponding name of the molecule was inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). The changes in ITIH4 levels correlated with those in the neonatal metabolic indices. By establishing the Fisher discriminant function equation for the GDM group, the difference in sample distribution and mean value of the two groups could be observed directly. Abbreviations: GDM: gestational diabetes mellitus; FPG: fasting plasma glucose; MB-WCX: weak cation exchange magnetic beads; MALDI-TOF MS: matrix-assisted laser desorption ionization time-of-flight mass spectrometry; m/z: mass charge ratio; LC-MS: liquid chromatography-tandem mass spectrometry; glycosylated hemoglobin (HbA1c); PPG: postprandial plasma glucose; ITIH4: inter-alpha-trypsin inhibitor heavy chain H4; IR: insulin resistance; NFPG: neonatal fasting plasma glucose; NH: neonatal height; NW: neonatal weight; BMI: body mass index; RPL: recurrent pregnancy loss; OGTT: oral glucose tolerance test; ADA: American Diabetes Association; LIS: Laboratory Information System

Determination of Urinary Gluten Immunogenic Peptides to Assess Adherence to the Gluten-Free Diet: A Randomized, Double-Blind, Controlled Study.

INTRODUCTION:The adherence to a gluten-free diet (GFD) is a trending topic in the management of celiac disease. The aim of our study was to evaluate the diagnostic performance of urinary gluten immunogenic peptides (GIP) determination to detect gluten contamination of the GFD.METHODS:In study A, 25 healthy adults on a standard GFD performed 6 gluten challenges (0, 10, 50, 100, 500, and 1,000 mg) with quantification of urinary GIP before (T0) and during the following 24 hours. In study B, 12 participants on a gluten contamination elimination diet underwent urinary GIP determination at T0 and after challenge with 5 or 10 mg gluten. Urine GIP concentration was determined by an immunochromatographic assay.RESULTS:In study A, 51 of 150 baseline urine samples were GIP+ on GFD and 7 of 17 were GIP+ after the zero-gluten challenge, whereas only 55 of 81 were GIP+ after the 10–1,000 mg gluten challenges. There was no significant change in the 24-hour urinary GIP when increasing gluten from 10 to 1,000 mg. In study B, 24 of 24 baseline urine samples were GIP−, whereas 8 of 24 were GIP+ after 5 or 10 mg of gluten.DISCUSSION:Traces of gluten in the standard GFD may cause positivity of urinary GIP determination, whereas a false negativity is common after a gluten intake of 10–1,000 mg. Owing to the impossibility of standardizing the test in normal conditions, it seems unlikely that urinary GIP determination may represent a reliable tool to assess the compliance to the GFD of patients with celiac disease or other gluten-related disorders.

Timeline of Changes in Biomarkers Associated with Spinal Cord Injury-Induced Polyuria.

Deficits in upper and lower urinary tract function, which include detrusor overactivity, urinary incontinence, detrusor-sphincter dyssynergia, and polyuria, are among the leading issues that arise after spinal cord injury (SCI) affecting quality of life. Given that overproduction of urine (polyuria) has been shown to be associated with an imbalance in key regulators of body fluid homeostasis, the current study examined the timing of changes in levels of various relevant hormones, peptides, receptors, and channels post-contusion injury in adult male Wistar rats. The results show significant up- or downregulation at various time points, beginning at 7 days post-injury, in levels of urinary atrial natriuretic peptide, serum arginine vasopressin (AVP), kidney natriuretic peptide receptor-A, kidney vasopressin-2 receptor, kidney aquaporin-2 channels, and kidney epithelial sodium channels (β- and γ-, but not α-, subunits). The number of AVP-labeled neurons in the hypothalamus (supraoptic and -chiasmatic, but not paraventricular, nuclei) was also significantly altered at one or more time points. These data show significant fluctuations in key biomarkers involved in body fluid homeostasis during the post-SCI secondary injury phase, suggesting that therapeutic interventions (e.g., desmopressin, a synthetic analogue of AVP) should be considered early post-SCI.

SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: An in-silico proof-of-principle of proteomics-based drug repurposing.

Severe COVID‐19 is reflected by significant changes in urine peptides. Based on this observation, a clinical test predicting COVID‐19 severity, CoV50, was developed and registered as in vitro diagnostic in Germany. We have hypothesized that molecular changes displayed by CoV50, likely reflective of endothelial damage, may be reversed by specific drugs. Such an impact by a drug could indicate potential benefits in the context of COVID‐19. To test this hypothesis, urinary peptide data from patients without COVID‐19 prior to and after drug treatment were collected from the human urinary proteome database. The drugs chosen were selected based on availability of sufficient number of participants in the dataset (n > 20) and potential value of drug therapies in the treatment of COVID‐19 based on reports in the literature. In these participants without COVID‐19, spironolactone did not demonstrate a significant impact on CoV50 scoring. Empagliflozin treatment resulted in a significant change in CoV50 scoring, indicative of a potential therapeutic benefit. The study serves as a proof‐of‐principle for a drug repurposing approach based on human urinary peptide signatures. The results support the initiation of a randomized control trial testing a potential positive effect of empagliflozin for severe COVID‐19, possibly via endothelial protective mechanisms.

PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA?

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD01)1 Sep 2021PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA? Sang Wook Lee, Woong Bin Kim, Si Hyun Kim, Ji Kang Yun, and Young Ho Kim Sang Wook LeeSang Wook Lee More articles by this author , Woong Bin KimWoong Bin Kim More articles by this author , Si Hyun KimSi Hyun Kim More articles by this author , Ji Kang YunJi Kang Yun More articles by this author , and Young Ho KimYoung Ho Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001965.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since urine is not sterile, inflammatory reactions caused by dysbiosis of urinary microbiota may induce interstitial cystitis. A study was conducted to find out whether BD2, one of antimicrobial peptides in urine, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC), compared to macrophage migration inhibitory factor (MIF). METHODS: Urine samples were assayed for BD2 and MIF by enzyme-linked immunosorbent assays (ELISA). Urine samples from three female groups were examined: healthy controls (N=34, Group I), non-ulcerative IC (N=40, Group II), and ulcerative IC (N=68, Group III). Urine samples were collected via transurethral catheter all patients with IC. Cystoscopy with diagnostic and therapeutic hydrodistention was applied a to Group II & III patients. The National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) criteria were applied to the patients with endoscopic clinical diagnosis of Painful bladder syndrome/IC. The mast cell counts criteria proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) were contrasted and results were compared. RESULTS: Based on urinary specimens from a total of 142 patients, BD2 expressed 18-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. MIF levels were 31-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. The enhanced secretion of BD-2 exhibited a strong correlation with the increased mast cell counts associated with bladder IC pathology. CONCLUSIONS: Enhanced urinary secretion of BD2 from ulcerative IC patients demonstrated relatively robust levels to be used as potential biomarkers, and associated with clinical phenotypes. Moreover, the increased urinary level of anti-microbial peptide BD2 may suggest a new possibility of diagnosis caused by dysbiosis of urinary microbiota in ulcerative IC. Source of Funding: This work was supported by the “Soonchunhyang University Research Fund” © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e31-e32 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sang Wook Lee More articles by this author Woong Bin Kim More articles by this author Si Hyun Kim More articles by this author Ji Kang Yun More articles by this author Young Ho Kim More articles by this author Expand All Advertisement Loading ...

Identification of urinary peptides associated with allergic rhinitis

BackgroundWhether in the world or in China, allergic rhinitis (AR) is a disease that seriously affects people's daily life. However, the current diagnostic methods for AR still have certain limitations. Adopt matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for proteomics detection makes it possible to screen for high-throughput biomarkers. This study intends to use this technology to analyze the urine proteomics of AR patients to find potential biomarkers for AR diagnosis. Materials and methodsUrine and clinical data were collected from 60 patients with AR and 60 healthy controls. MALDI-TOF-MS based on weak cation exchange magnetic beads was used to obtain and analyze the urine peptide profiles between AR patients and healthy controls. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of identified peptides and proteins. ResultsThe results revealed significantly different expressions of nine peptide peaks between AR and healthy controls (ROC area under the curve [AUC], 0.660–0.780). We constructed a diagnostic model containing seven proteins identified from the above-mentioned peptide peaks. The AUC of the seven peptides panel for AR diagnosis was 0.882 with 75.0% sensitivity and 90.0% specificity. ConclusionsThe seven peptides diagnostic model established in this study had high specificity and moderate sensitivity in the diagnosis of AR. MALDI-TOF MS is a potential tool for diagnosing AR by the use of urine samples.

CD99 and polymeric immunoglobulin receptor peptides deregulation in critical COVID-19: A potential link to molecular pathophysiology?

Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID‐19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR‐confirmed COVID‐19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6–8 and 66 at WHO stages 1–3 COVID‐19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha‐1‐antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID‐19. The clinical corollary is that COVID‐19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha‐1‐antitripsin, may represent a valid and effective therapeutic approach in COVID‐19, targeting improvement of endothelial integrity.