Urine soluble CD163 (sCD163) as biomarker in glomerulonephritis: stability, reference interval and diagnostic performance

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anne J. Nielsen ◽  
Marlene C. Nielsen ◽  
Henrik Birn ◽  
Per Ivarsen ◽  
Holger J. Møller ◽  
...  
Keyword(s):  
Crescentic Glomerulonephritis ◽  
Reference Interval ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Reference Limit ◽  
Urine Albumin ◽  
Analytical Stability ◽  
Different Types ◽  
Upper Reference Limit ◽  
Better Than

AbstractObjectivesSoluble (s) CD163 is a well-established macrophage biomarker, and recent data suggests urine sCD163 to reflect disease activity in crescentic glomerulonephritis (GN). Other types of GN may also be associated with glomerular inflammation but the potential usefulness of urine sCD163 as a general biomarker of GN remains unaddressed.MethodsAn in-house sCD163 enzyme-linked immunosorbent assay (ELISA) was validated for urinary use and compared to a frequently used commercial ELISA. The pre-analytical stability of urine sCD163 was assessed and a reference interval was established according to the CLSI guidelines using specimens from 253 healthy individuals. Urine samples from 64 patients with different types of renal disorders were also analysed.ResultsUrine sCD163 was highly stable during storage. An upper reference limit of 5.1 μg/L (1.9 μg/mmol, normalised to creatinine) was established using the in-house ELISA. Urine sCD163 was generally increased in GN patients (3.9 μg/mmol, p<0.0001, AUROC=0.97) and decreased upon treatment, but did not perform better than urine albumin (AUROC=1.00). Patients with proliferative GN had higher urine sCD163/albumin (p=0.0001) ratio. The commercial assay had a higher detection limit, and patient levels were 4–6 times lower than in the in-house assay.ConclusionsUrine sCD163 is a stable biomarker that can be measured with acceptable accuracy using our in-house ELISA. Its pre-analytical characteristics makes it a reliable biomarker and our findings point towards the use of urine sCD163 as a biomarker of specific subtypes of GN.

Albumin and calcium reference interval using healthy individuals and a data-mining approach

2020 ◽  
Vol 57 (5) ◽  
pp. 373-381 ◽  
Author(s):  
N Jassam ◽  
A Luvai ◽  
D Narayanan ◽  
D Turnock ◽  
G Lee ◽  
...  
Keyword(s):  
Metrological Traceability ◽  
Reference Interval ◽  
Reference Population ◽  
Reference Intervals ◽  
Healthy Individuals ◽  
Reference Limit ◽  
Common Reference ◽  
Age Related ◽  
Upper Reference Limit ◽  
Analytical Platforms

Background Harmonization of reference intervals for analytes that have a sound calibration and metrological traceability is a widely recommended practice. The UK Pathology Harmony has recently harmonized reference intervals for calcium and albumin. In this study, we have determined the reference intervals for calcium and albumin on the UK’s most commonly used analytical platforms. Method A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. A second indirect population was collected from 14 primary care setting and measured in laboratories using various analytical platforms and methods (Roche, Abbott, Beckman and Siemens analytical platforms). Results In total, 299 subjects were recruited; the central 95th centile values for calcium for three out of four analytical platforms were in a close agreement with UK Pathology Harmony reference intervals of 2.2–2.6 mmol/L. Reference intervals of BCG methods from both cohorts and irrespective of analytical platforms were higher for both lower and upper reference limits than those for BCP. In comparison, the indirect study showed an age-related variation. The younger population reference intervals varied by up to 5.7% at the lower reference limit and up to 12% at the upper reference limit compared with Pathology Harmony reference intervals, and the older population showed a variation of up to 14% at both limits. Conclusion While calcium reference intervals can be a subject for harmonization, albumin reference intervals studied showed large variation which is unsupportive of embracing a common reference interval for albumin.

scholarly journals Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Anke Heida ◽  
Anneke C. Muller Kobold ◽  
Lucie Wagenmakers ◽  
Koos van de Belt ◽  
Patrick F. van Rheenen
Keyword(s):  
Characteristic Curve ◽  
Reference Value ◽  
Reference Interval ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Healthy Controls ◽  
Reference Limit ◽  
School Aged Children ◽  
Activated Neutrophils ◽  
Upper Reference Limit

AbstractBackground:Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls.Methods:In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5–19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (InflamarkResults:The upper reference limit in healthy children was 0.75 μg/g (90% confidence interval: 0.30–1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 μg/g [interquartile range (IQR) 2.5–11.6] compared to healthy controls [0.22 μg/g (IQR<0.22); p<0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 μg/g (sensitivity 93%; specificity 97%).Conclusions:Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from non-organic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers.

scholarly journals Cerebrospinal Fluid Protein Concentration in Healthy Older Japanese Volunteers

2021 ◽  
Vol 18 (16) ◽  
pp. 8683
Author(s):  
Tatsuya Yoshihara ◽  
Masayoshi Zaitsu ◽  
Kazuya Ito ◽  
Ryuzo Hanada ◽  
Eunhee Chung ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Asian Population ◽  
Reference Interval ◽  
Reference Limit ◽  
Neurological Emergencies ◽  
Precise Diagnosis ◽  
The Mean ◽  
Upper Reference Limit ◽  
Age Range ◽  
Cerebrospinal Fluid Protein

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.

scholarly journals Colorectal Carcinoma Affected Patients Are Significantly Poor Responders Against the Oncogenic JC Polyomavirus

2021 ◽  
Vol 12 ◽  
Author(s):  
Elena Torreggiani ◽  
Ilaria Bononi ◽  
Silvia Pietrobon ◽  
Elisa Mazzoni ◽  
Giovanni Guerra ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Synthetic Peptides ◽  
Enzyme Linked Immunosorbent Assay ◽  
Poor Responders ◽  
Igg Antibodies ◽  
Healthy Individuals ◽  
Jc Polyomavirus ◽  
Oncogenic Potential ◽  
Different Types ◽  
Immunological Dysfunction

BackgroundMany investigations reported the association between human tumors and JCPyV, a polyomavirus with oncogenic potential. The association has been supported by studies that found JCPyV footprints in CRC and gliomas of different types. Indeed, JCPyV footprints including its nucleic acids and Tag oncoprotein have been revealed in CRC tissues.MethodsHerein, sera from colorectal carcinoma (CRC) affected patients and healthy individuals (HS), employed as control, were analysed for immunoglobulin G (IgG) antibodies against specific JCPyV viral capsid protein 1 (VP1) antigens. The investigation was carried out employing an innovative immunological assay. Indeed, an indirect enzyme-linked immunosorbent assay (ELISA) with JCPyV VP1 mimotopes was used. JCPyV VP1 mimotopes consisted of synthetic peptides mimicking VP1 epitopes.ResultsSera from CRC affected patients, evaluated using indirect ELISAs with synthetic mimotopes, showed a significant lower prevalence of IgG antibodies against JCPyV VP1 mimotopes (26%) compared to HS (51%), p&lt;0.005. These data were confirmed by another method, the hemagglutination inhibition (HAI) assay. Altogether these results, i.e. the prevalence of serum IgG antibodies against JCPyV VP1 mimotopes from patients with CRC is approximately 50% lower than in HS, are of interest.DiscussionOur data suggest that patients with CRC are significantly poor responders against JCPyV VP1 antigens. It is possible that CRC patients are affected by a specific immunological deregulation. This immunological dysfunction, revelled in CRC patients, may account for their predisposition to the colorectal carcinoma onset.

scholarly journals Evaluation of a sandwich enzyme-linked immunosorbent assay for the measurement of serum heart fatty acid-binding protein

2002 ◽  
Vol 39 (4) ◽  
pp. 404-405 ◽  
Author(s):  
Franca Pagani ◽  
Roberto Bonora ◽  
Graziella Bonetti ◽  
Mauro Panteghini
Keyword(s):  
Fatty Acid ◽  
Immunosorbent Assay ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Characteristic Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fatty Acid Binding ◽  
Reference Limit ◽  
Acid Binding Protein ◽  
Upper Reference Limit

Background: We evaluated the sandwich enzyme-linked immunosorbent assay (ELISA) MARKIT®-M for the determination of heart fatty-acid-binding protein (H-FABP). Results and Conclusions: The between-run coefficient of variation of this assay was <3·9 and it showed good correlation with a previously established ELISA method. The upper reference limit in 30 healthy individuals was 6·1 μg/L. Admission serum H-FABP was evaluated against myoglobin in 41 patients with suspected myocardial infarction (onset of symptoms ≤ 5 h). H-FABP showed the same diagnostic efficiency as myoglobin [area (standard error) under the receiver operating characteristic curve: 0·798 (0·079) for H-FABP, 0·771 (0·085) for myoglobin, P = 0·55]. However, using the upper reference limit as decision cut-off, the sensitivity for H-FABP [91%; 95% confidence interval (CI): 76-98%] was significantly ( P = 0·019) higher than that of myoglobin (65%; 95% CI: 47-80%).

scholarly journals Disappearance Rate of Catecholamines, Total Metanephrines, and Neuropeptide Y from the Plasma of Patients after Resection of Pheochromocytoma

2001 ◽  
Vol 47 (6) ◽  
pp. 1075-1082 ◽  
Author(s):  
Eric Grouzmann ◽  
Marc Fathi ◽  
Michel Gillet ◽  
Antoine de Torrenté ◽  
Claudia Cavadas ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Plasma Concentrations ◽  
Amperometric Detection ◽  
Reference Interval ◽  
Diagnostic Value ◽  
Relative Increase ◽  
Time Curve ◽  
Reference Limit ◽  
Upper Reference Limit ◽  
Total Sulfate

Abstract Background: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. Methods: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration–time curve over 120 min. Results: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 ± 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. Conclusions: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

scholarly journals Choice of Statistical Tools for Outlier Removal Causes Substantial Changes in Analyte Reference Intervals in Healthy Populations

2020 ◽  
Vol 66 (12) ◽  
pp. 1558-1561 ◽  
Author(s):  
Peter E Hickman ◽  
Gus Koerbin ◽  
Julia M Potter ◽  
Nicholas Glasgow ◽  
Juleen A Cavanaugh ◽  
...  
Keyword(s):  
Statistical Methods ◽  
Population Studies ◽  
Large Population ◽  
Large Body ◽  
Reference Interval ◽  
Reference Intervals ◽  
Outlier Removal ◽  
Reference Limit ◽  
Statistical Measures ◽  
Upper Reference Limit

Abstract Background Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased. Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons. Methods We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes. Results Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more. Conclusions For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.

Rapid determination of serum myoglobin with a routine chemistry analyzer

1993 ◽  
Vol 39 (4) ◽  
pp. 653-658 ◽  
Author(s):  
A J Bakker ◽  
D A Boymans ◽  
D Dijkstra ◽  
J P Gorgels ◽  
R Lerk
Keyword(s):  
Predictive Value ◽  
Rapid Determination ◽  
Reference Interval ◽  
High Dose ◽  
Reference Limit ◽  
Hook Effect ◽  
Upper Limit ◽  
Upper Reference Limit ◽  
Serum Myoglobin

Abstract A turbidimetric immunoassay system (Turbitime system, Behringwerke AG) allows rapid determination of myoglobin in serum. We adapted the reagents for this myoglobin assay (Turbiquant myoglobin) for use with a Hitachi 717 analyzer. No high-dose hook effect was observed up to 15,000 micrograms/L. Interassay CVs were 4.6% (mean = 72.0 micrograms/L; n = 9) and 2.5% (mean = 365.6 micrograms/L; n = 11). The calibration curve was stable for at least 1 month. Hemolysis did not interfere, and turbidity from lipemia interfered only when absorbance exceeded 2.0 A. Results of this method (y) correlated well with those by the Turbitime method (y = 1.256x - 44.1 micrograms/L; n = 91; r = 0.991) and by a commercially available radioimmunoassay (Byk-Sangtec; y = 0.739x - 42.2 micrograms/L; n = 94; r = 0.991). The upper limit (95th percentile) of the reference interval for myoglobin was estimated at 57.9 micrograms/L. The positive predictive value for results of myoglobin at admission was 89% with this upper reference limit and 99% with 100 micrograms/L, whereas the negative predictive value was about 60% for both limits.

scholarly journals Routine α-Amylase Assay Using Protected 4-Nitrophenyl-1,4-α-d-maltoheptaoside and a Novel α-Glucosidase

2000 ◽  
Vol 46 (5) ◽  
pp. 644-649 ◽  
Author(s):  
Klaus Lorentz
Keyword(s):  
Amylase Activity ◽  
Reference Method ◽  
Reference Interval ◽  
Lag Phase ◽  
Reference Limit ◽  
Independent Constant ◽  
Increased Sensitivity ◽  
Upper Reference Limit ◽  
Manual Performance ◽  
Age And Sex

Abstract Background: In contrast to numerous methods for measuring α-amylase activity, the approved IFCC reference method offers an invariable time-independent constant product pattern, thus avoiding possibly changing stoichiometric calculations. However, reference methods do not lend themselves to routine use, so that such methods need to be modified. Methods: Ethylidene-blocked 4-nitrophenylmaltoheptaoside (EPS-G7) is degraded to glucose and 4-nitrophenol in a coupled assay with a bacterial α-glucosidase under the following measurement conditions: 3.5 mmol/L EPS-G7, 7.1 kU/L α-glucosidase, 70 mmol/L sodium chloride, 1 mmol/L calcium chloride, 50 mmol/L HEPES, pH 7.15, at 37 °C. The increase of absorbance is continuously monitored for 3 min at 405 nm after a lag phase of 2 min. Results: Catalytic concentrations up to 15-fold higher than the upper reference limit can be determined without dilution. Precision studies in manual performance show CVs of 1.4–2.6% (within-run) and 1.9–2.8% (day-to-day). There was no interference from 100 mmol/L glucose, 30 mmol/L triacylglycerols, 610 μmol/L bilirubin, and 2.95 g/L hemoglobin. The method closely correlates with other chromogenic assays. The preliminary 0.95 reference interval for adults, not dependent on age and sex, is 33.6–96.2 U/L. Conclusion: The procedure is a robust adaptation of the reference method to routine use at 37 °C with increased sensitivity, fewer interferences, and reduced cost.

scholarly journals Immunoassay for Quantifying Squamous Cell Carcinoma Antigen in Serum

2010 ◽  
Vol 56 (9) ◽  
pp. 1496-1499 ◽  
Author(s):  
J Alan Erickson ◽  
Jun Lu ◽  
Jeffery J Smith ◽  
Joshua A Bornhorst ◽  
David G Grenache ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Reference Interval ◽  
Microtiter Plate ◽  
Squamous Cell Carcinoma Antigen ◽  
Reference Limit ◽  
Automated Assay ◽  
The Us ◽  
Upper Reference Limit

BACKGROUND Although the benefits of quantifying serum squamous cell carcinoma antigen (SCCa) have been reported, SCCa reagents were no longer available in the US by the late 1990s. Because SCCa quantification still has demonstrated clinical utility, we developed and validated a microtiter plate–based ELISA for measuring SCCa in serum. METHODS We coated microtiter strips overnight with capture anti-SCCa monoclonal antibody, washed the wells, added blocking buffer, and lyophilized the strips. For detection, we used a biotinylated anti-SCCa detection antibody, streptavidin/horseradish peroxidase conjugate, and tetramethylbenzidine/H2O2 substrate. A novel blocking reagent against human antimouse antibodies (HAMA) was evaluated. A reference interval was established with sera from healthy individuals and was confirmed in smokers. RESULTS The assay was linear to 40 μg/L SCCa (slope, 1.00; y intercept, 0.695; R2, 0.996) with a detection limit of 0.3 μg/L. The intraassay imprecision results [mean (CV)] were 2.5 μg/L (3.4%), 18.0 μg/L (3.0%), and 30.7 μg/L (2.4%); interassay imprecision results were 2.0 μg/L (9.9%), 20.0 μg/L (7.6%), and 36.3 μg/L (3.5%). A correlation analysis against an established automated assay generated a slope of 0.976 and a y intercept of −0.193 μg/L (r2 = 0.916). An upper reference limit of 2.1 μg/L SCCa was established at 95% confidence level, with no difference observed in smokers. No correlation between SCCa concentration and age was observed (r2 = 0.0003). At a blocking reagent concentration of 5 mg/L, HAMA interference was eliminated in 3 samples known to produce falsely increased SCCa results. CONCLUSIONS This SCCa ELISA demonstrates acceptable performance characteristics for quantifying serum SCCa and is effective in eliminating HAMA interference.

Sign in / Sign up

Export Citation Format

Share Document