Annals Of Clinical Biochemistry[JOURNAL]
Sun
200 papers
Analysis of first-trimester maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels as a potential non-invasive biomarker for fetal aneuploidy and NTDs.
E K, Selvarajan S, Senthil Kumar D … +2 more , K S, K S S
Ann Clin Biochem · 2026 Mar · PMID 40728842 · Publisher ↗
ObjectivesChromosomal abnormalities and congenital anomalies have huge impact on infant mortality and morbidity. The combined incidence affects approximately 1 per 1000 pregnancies. Current diagnostic modalities include...
ObjectivesChromosomal abnormalities and congenital anomalies have huge impact on infant mortality and morbidity. The combined incidence affects approximately 1 per 1000 pregnancies. Current diagnostic modalities include ultrasonography and biomarkers like Beta hCG, PAPP-A and Alpha fetoprotein which have limitations due to their varied sensitivity and specificity in aneuploidy and NTD detection. PCSK9, a proprotein converters appears to have an escalating role in neurogenesis, neuronal differentiation and neurological diseases apart from its role in lipid metabolism. This study estimates serum PCSK9 levels in pregnant women with normal gestation and those with high risk for Aneuploidy and NTDs.MethodsThis prospective case control study included 40 pregnant women with high risk of aneuploidy and NTDs (cases) diagnosed by prenatal screening with ultrasonography findings, Beta HCG, PAPP-A and 40 pregnant women with a healthy singleton pregnancy (controls). Statistical analyses were performed in SPSS software version 16. Fetal and maternal characteristics, serum Beta HCG, PAPP-A, PCSK-9 and aneuploidy risk scores were compared between two groups.ResultsThis study observed significant difference in Beta HCG, PAPP-A and PCSK9 levels between the groups ( < .05). The PCSK9 levels were lower in cases [82.95 (70.41-90.74)] than control group [123.84 (102.515-152.70)]. PCSK9 levels <96.8 ng/mL had an 85% sensitivity and specificity. Further PCSK9 correlated with Trisomy 21 risk score and Beta HCG ( < .05).ConclusionsMaternal serum PCSK9 is decreased in high-risk pregnancy during first trimester. With 85% sensitivity, the marker could be a reliable screening tool during prenatal screening which needs further validation.
Validation of the Japan Society of Clinical Chemistry (JSCC) recommended reference measurement procedure for glycated albumin determination.
Meguro S, Iwasaki Y, Ueda J … +9 more , Okahashi M, Kume Y, Kohzuma T, Shimizu E, Takeda H, Hirayama S, Hosoba E, Nakagawa T, Sato A
Ann Clin Biochem · 2026 Mar · PMID 40728841 · Publisher ↗
BackgroundTo clarify the fundamental characteristics of the Japan Society of Clinical Chemistry reference measurement procedure (JSCC RMP) for glycated albumin (GA), an additional performance study was performed and the...
BackgroundTo clarify the fundamental characteristics of the Japan Society of Clinical Chemistry reference measurement procedure (JSCC RMP) for glycated albumin (GA), an additional performance study was performed and the correlation between the HPLC method and JSCC RMP was re-evaluated.MethodsRepeatability, detection limit, addition recovery, uncertainty of measurement, inter-laboratory comparison, correlation between JSCC RMP and HPLC method were evaluated.ResultsThe coefficient of variation (CV) of the total repeatability for the nine pretreated samples including isotope dilution and hydrolysis, defining that the averages of each of nine MS measurement samples are independent measurement vials, was 1.0%( = 9). The limit of detection and Quantification of the GA values were 7.4 and 29.5 mmol/mol, respectively. Addition recovery rates were 99.6%-100.4%. The strong correlation (r = 0.999) of measured six serum samples between two laboratories was observed. Certified values and expanded uncertainties for JCCRM 611-2 (M, H, HH) using the JSCC RMP were as follows: JCCRM 611-2M: 232 and 9 mmol/mol, JCCRM611-2H: 359 and 14 mmol/mol, JCCRM611-2HH: 556 and 22 mmol/mol, respectively. The regression equation obtained using the Passing-Bablok method was GA (%) = 0.0523 × GA (mmol/mol) + 1.315.ConclusionThe basic performance of the JSCC reference procedure for GA measurement was good, and similar results were obtained at other facilities, so it was considered to be robust and suitable as a reference method for GA measurement. Additionally, an equation was established to convert JSCC RMP (mmol/mol) values to the HPLC% values used in clinical practice.
Erratum to "Current practice and recommendations for managing transgender patient data in clinical laboratories in the United Kingdom and Republic of Ireland".
Ann Clin Biochem · 2026 Jan · PMID 40667627 · Publisher ↗
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Response to Cearcero-Marin D, Martinez-Zamoran L, Gisbert-Alonso A, et al. Metamizole (dipyrone) as an interferent in biochemical assays. Ann Clin Biochem 2025.
Sonntag O
Ann Clin Biochem · 2026 Jan · PMID 40642779 · Publisher ↗
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Relationships of serum levels of tocilizumab to interleukin-6 and endogenous markers of CYP3A activity in patients with rheumatoid arthritis.
Mochizuki T, Shibata K, Naito T … +3 more , Shimoyama K, Ogawa N, Kawakami J
Ann Clin Biochem · 2026 Jan · PMID 40562694 · Publisher ↗
BackgroundTocilizumab co-administration and inflammatory conditions potentially alter the activity of cytochrome P450 (CYP) 3A4 by modulating the interleukin-6 (IL-6) signaling pathway in patients with rheumatoid arthrit...
BackgroundTocilizumab co-administration and inflammatory conditions potentially alter the activity of cytochrome P450 (CYP) 3A4 by modulating the interleukin-6 (IL-6) signaling pathway in patients with rheumatoid arthritis (RA). This study aimed to evaluate the correlations of serum levels of tocilizumab with IL-6 and CYP3A activity in RA.MethodsRA patients (n = 35) with controllable disease activity using intravenous or subcutaneous tocilizumab were enrolled. Serum tocilizumab was monitored at the trough point after reaching steady-state. Serum levels of IL-6, its soluble receptor (sIL-6R), 4β-hydroxycholesterol (4β-OHC), and 25-hydroxyvitamin D (25-OHD) and CYP3A5 genotype were determined.ResultsThe RA patients had a wide variation of serum tocilizumab level (interquartile range, 9.8-24.6 µg/mL). Tocilizumab treatment led to abnormally high levels of serum IL-6 and sIL-6R. The serum level of tocilizumab was correlated with that of IL-6 but not sIL-6R. In the tocilizumab-treated RA patients, the median serum levels of 4β-OHC and 25-OHD were 36.7 and 17.7 ng/mL, respectively, and no correlations with the serum level of tocilizumab were observed. CYP3A5 genetic polymorphisms were not also associated with the serum level of 4β-OHC. RA patients with the allele exhibited a correlation between serum levels of tocilizumab and 4β-OHC, while those with did not.ConclusionsTocilizumab treatment raised the serum IL-6 level in a concentration-dependent manner. In the RA patients with functional CYP3A5 protein, the serum tocilizumab level partially explained the interindividual variation in CYP3A activity.
Application of ergosterol as a maitake mushroom intake biomarker.
Kuwabara N, Jogi EM, Kato M … +8 more , Masuda Y, Konishi M, Yamasaki K, Ohata S, Kato S, Hashimoto M, Sato S, Nakagawa S
Ann Clin Biochem · 2026 Jan · PMID 40562565 · Publisher ↗
BackgroundDyslipidemia is a lifestyle-related disease; therefore, cholesterol biosynthesis inhibitors in foods can be easily ingested on a daily basis and are effective in aiding treatment and prevention. To assess the i...
BackgroundDyslipidemia is a lifestyle-related disease; therefore, cholesterol biosynthesis inhibitors in foods can be easily ingested on a daily basis and are effective in aiding treatment and prevention. To assess the impact of this diet on health, it is of the essential thing that food intake can be properly measured, and it is important to find biomarkers of food intake. Previously, we reported that ergosterol, which is present in mushrooms, inhibits cholesterol biosynthesis. In this study, we measured serum ergosterol levels in healthy participants who consumed maitake mushroom bread to confirm actual ingestion of maitake mushrooms.MethodsSerum samples from healthy participants who consumed maitake mushroom bread ( = 24) or normal bread without maitake mushroom (placebo, = 26) were analysed for ergosterol levels using liquid chromatography-tandem mass spectrometry with diene derivatization.ResultsIn the placebo group, there was no significant difference in ergosterol concentrations between baseline (before consumption) and 18 weeks. In contrast, the ergosterol concentration was 5-fold higher at 18 weeks than at baseline in the maitake mushroom bread-intake group.ConclusionMaitake mushroom bread intake for 18 weeks significantly increased serum ergosterol levels in healthy participants, suggesting that ergosterol is useful as a biomarker of mushroom intake.
Diurnal variation in salivary testosterone independent of food consumption.
Fenn J, Gill H, Kalaria T … +5 more , Starbrook L, Ford L, Sharrod-Cole H, Ford C, Gama R
Ann Clin Biochem · 2026 Jan · PMID 40555679 · Publisher ↗
BackgroundWe previously reported that salivary testosterone (Sal T) decreased following a morning meal but concluded that this decrease could be a postprandial effect or an inherent circadian rhythm or both. Since no stu...
BackgroundWe previously reported that salivary testosterone (Sal T) decreased following a morning meal but concluded that this decrease could be a postprandial effect or an inherent circadian rhythm or both. Since no studies describing diurnal variations in Sal T have considered the effect of meals, we investigated the temporal variation of Sal T independent of food consumption.MethodsSalivary samples were collected from 17 males at 09.00 h, 10.00 h, and 11.00 h and then at 22.00 h, 23.00 h, and 24.00 h following an 8 h fast for each collection period.ResultsMean (standard deviation) Sal T concentrations were 191.2 (56.68) pmol/L at 09.00 h, 174.2 (53.29) pmol/L at 10.00 h, 168.1 (52.61) pmol/L at 11.00, 120.2 (46.04) pmol/L at 22.00 h, 130.3 (35.72) pmol/L at 23.00 h and 125.1 (29.75) pmol/L at 24.00 h. Sal T at 09.00 h was higher ( < .05) than at all other time points. Sal T at 10.00 h was similar ( = .65) to that at 11.00 h and both were higher ( < .05) compared to all evening time points. Although some patients exhibited a nadir in Sal T at 22:00 followed by an increase, overall evening levels were not significantly different ( > .80).ConclusionWe report an inherent circadian rhythm in Sal T with higher levels in the morning than evening and report for the first time that it is independent of food consumption.
A method comparison of the Roche intact PTH method versus the Roche whole PTH (1-84) method: Examining the differences based on eGFR.
E B, Pj T, Rk C … +2 more , Mj M, M K
Ann Clin Biochem · 2026 Mar · PMID 40551390 · Publisher ↗
AimThird-generation whole PTH (1-84) parathyroid hormone (PTH) assays do not recognize the PTH 7-84 fragment whereas second-generation (intact) assays detect both 1-84 and 7-84 PTH fragments. This study aimed to compare...
AimThird-generation whole PTH (1-84) parathyroid hormone (PTH) assays do not recognize the PTH 7-84 fragment whereas second-generation (intact) assays detect both 1-84 and 7-84 PTH fragments. This study aimed to compare the second-generation Roche intact PTH method with the third-generation Roche whole PTH (1-84) method, examining differences based on estimated glomerular filtration rate (eGFR).MethodsThe intact PTH method and whole PTH (1-84) method were compared using 100 serum samples selected across eGFR quintiles for chronic kidney disease (CKD) stages 1-5 in accordance with Kidney Disease: Improving Global Outcomes (KDIGO).ResultsMethod comparison based on eGFR showed that differences between both PTH methods were not significant at eGFR >60 mL/min/1.73 m. There was a statistically significant difference at eGFR <60 mL/min/1.73 m. The whole PTH (1-84) method produced lower results as eGFR decreased: CKD Stage 3 (mean difference: -21%; 95% confidence interval: -16 to -26%) to CKD Stage 5 (mean difference: -46%; 95% confidence interval: -40 to -52%).ConclusionsDifferences observed between the two assays may be due to second-generation PTH assays overestimating PTH concentration by measuring both 1-84 PTH and C-terminal fragments, notably PTH (7-84) in patients with significant renal impairment. The whole PTH (1-84) assay may be used to monitor metabolic bone disease risk. Initial dual reporting of PTH by both methods is recommended for eGFR <60 mL/min to educate users due to the difference in results.
The influence of haemolysis in patient samples on biochemical tests analysed using Roche Cobas 8000 analyzer.
Hung YE, Chiu YI, Shiesh SC … +4 more , Lin YC, Cheng CL, Hsueh KY, Lin WL
Ann Clin Biochem · 2026 Jan · PMID 40551378 · Publisher ↗
BackgroundModern analyzers employ the haemolysis index (HI) to identify interference in biochemical assays, yet manufacturer-defined HI thresholds may be inappropriate for true haemolysis effects, resulting in unnecessar...
BackgroundModern analyzers employ the haemolysis index (HI) to identify interference in biochemical assays, yet manufacturer-defined HI thresholds may be inappropriate for true haemolysis effects, resulting in unnecessary sample rejections. This study aimed to validate these thresholds using non-simulated hemolyzed patient samples.MethodsPaired samples (hemolyzed primary and non-hemolyzed recollected) from 678 patients were analysed for haemolysis interference. Biochemical analytes and serum indices were measured using a Roche Cobas 8000 analyzer. Haemolysis effects on test results and lipaemia index (LI) were assessed. HI thresholds were derived from reference change value (RCV) limits and regression of HI versus percentage bias, then compared to the conventional 10% deviation criterion and Roche-defined cut-offs.ResultsSamples exhibited predominantly moderate haemolysis (72.3%, HI: 101-300). Strong HI correlations were observed for lactate dehydrogenase (51% change per 100-unit HI, = 0.6524, < .0001), potassium (14% per 100-unit HI, = 0.5630, < .0001), and sodium (-0.6% per 100-unit HI, = 0.5414, < .0001). Elevated biases exceeded the RCV for these analytes, plus ammonia, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, and bilirubin-direct, whereas sodium showed a clinically significant reduction at heavy haemolysis (HI 560). RCV-derived thresholds exhibited comparable or higher than 10% change and Roche cut-offs. The elevated LI in hemolyzed samples with HI greater than 100 decreased significantly after recollection.ConclusionsPatient-based haemolysis data indicated that biases for most analytes remain within clinically acceptable limits, suggesting the manufacturer's HI thresholds may overestimate interference, supporting lab-validated, RCV-based cut-offs enhance clinical relevance and decrease unnecessary sample rejection.
Clinical profile and utility of biomarkers in children with cobalamin (vitamin B12) deficiency: A cross-sectional study.
Sankar S, Srinivasan R, Bharadwaj V … +1 more , Devi S
Ann Clin Biochem · 2026 Jan · PMID 40551363 · Publisher ↗
BackgroundTo assess utility of novel biomarkers in diagnosing children with clinical cobalamin deficiency. Current practice uses total vitamin B12 levels to confirm diagnosis, which lacks sensitivity when used in isolati...
BackgroundTo assess utility of novel biomarkers in diagnosing children with clinical cobalamin deficiency. Current practice uses total vitamin B12 levels to confirm diagnosis, which lacks sensitivity when used in isolation.MethodsBetween November 2020 and September 2022, a prospective cross-sectional study was carried out in a tertiary teaching hospital. Children between 1 month and 18 years with clinical symptoms/at-risk of developing B12 deficiency were included. Relevant clinical and laboratory information (including total B12 and biomarker levels) was documented. Sensitivity and specificity of individual biomarkers were assessed using 4cB12, an indicator of functional B12 status. Version 4.2.1 of R language was used for statistical analysis.ResultsAnalysis was performed on 67 children. Anorexia, fatigue and behavioural abnormalities were among the leading clinical characteristics. 49% children had peripheral smear (PS) suggestive of cobalamin deficiency, and 43% had low total B12 levels. Among biomarkers, 85% children had low holotranscobalamin (HoloTC), and 73% and 55% had high methylmalonic acid (MMA) and elevated homocysteine (Hcy) levels, respectively. Sensitivity of total B12 was 51%, HoloTC 87%, MMA 83% and Hcy 64%. Combination of low HoloTC, macrocytosis and abnormal PS had 94% sensitivity while HoloTC with mean corpuscular volume (MCV) alone was 88% sensitive in detecting cobalamin deficiency.ConclusionLow total B12 levels lack sensitivity to diagnose cobalamin deficiency. Although combination of low HoloTC with abnormal smear and macrocytosis was found to have better sensitivity, reporting an abnormal smear is time consuming and requires skilled personnel. Combination of low HoloTC with macrocytosis has good sensitivity and can be considered a better screening tool for detecting B12 deficiency.
Variability in SHBG assays and the effect thereof on calculated estimates of free testosterone.
Walravens J, Adaway J, Reyns T … +7 more , Narinx N, Nyamaah JA, Antonio L, Kaufman JM, Keevil B, Fiers T, Lapauw B
Ann Clin Biochem · 2025 Nov · PMID 40500910 · Publisher ↗
BackgroundSerum free testosterone is commonly used as a parameter to evaluate testosterone exposure and is mostly calculated using mathematical approximations. As the principal testosterone-binding protein, SHBG concentr...
BackgroundSerum free testosterone is commonly used as a parameter to evaluate testosterone exposure and is mostly calculated using mathematical approximations. As the principal testosterone-binding protein, SHBG concentration is always included in such calculations. However, variability in SHBG measurements may affect reported SHBG levels and consequently free testosterone calculations. In this study, we re-evaluate the effects of SHBG assay choice and interlaboratory variability on calculated free testosterone (cFT).MethodsSerum samples from 113 men and 106 women were collected. SHBG levels were measured using three different SHBG immunoassays (Roche, Abbott and Siemens). Testosterone levels were measured using LC-MS/MS. Afterwards, cFT was calculated using the Vermeulen formula and measured directly. SHBG concentrations, and derived cFT concentrations, from different assays were compared. To simulate interlaboratory SHBG variability, measured levels were modified by 15% after which cFT was recalculated using the Vermeulen, Ly, Sartorius and Södergard formulae. The proportions of diagnoses of hypogonadism or hyperandrogenism were compared.ResultsAssessed SHBG assays showed very good conformity. The largest difference was 7%, between the Abbott and Siemens assay. The difference in cFT levels was at most 3% between the Abbott and Siemens assay. Interlaboratory variability affected the proportion of diagnoses depending on the used formula.ConclusionsOur results do not show large differences between SHBG assays and only minor effects on cFT levels. Therefore, SHBG assay choice is not expected to greatly influence clinical decision making. In contrast, interlaboratory variation in SHBG measurements and choice of formula might considerably affect cFT results and their interpretation.
The early diagnostic value of C-reactive protein (CRP) in deep sternal wound infection after cardiac surgery.
Jia S, Zhao J, Zhang J … +1 more , Jiang D
Ann Clin Biochem · 2026 Jan · PMID 40497326 · Publisher ↗
BackgroundThis study aimed to evaluate the early diagnostic value of C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), neutrophil ratio (NEUT%), and neutrophil-to-lymphocyte ratio (NLR) in pati...
BackgroundThis study aimed to evaluate the early diagnostic value of C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), neutrophil ratio (NEUT%), and neutrophil-to-lymphocyte ratio (NLR) in patients with deep sternal wound infection (DSWI).MethodsA retrospective case-control study was conducted on 241 patients who underwent cardiac surgery (30 patients with DSWI and 211 patients without DSWI). The differences in inflammatory markers were compared between the two groups at 5 time points (days 1, 4, 7, 10, and 14 after cardiac surgery), and the optimal cut-off values of the inflammatory factors independently correlated with DSWI were determined.ResultsUnivariate and multivariate logistic regression analyses showed that CRP on days 10 and 14, and PCT on day 10, were independently correlated with the occurrence of DSWI. The ROC curve showed the optimal cut-off value of them (CRP on day 10: AUC = 0.786, optimal cut-off point = 170.205 mg/L, sensitivity = 50.0%, specificity = 95.7%; CRP on day 14: AUC = 0.800, optimal cut-off point = 64.36 mg/L, sensitivity = 83.3%, specificity = 70.1%; PCT on day 10: AUC = 0.728, optimal cut-off point = 2.359 ng/mL, sensitivity = 43.3%, specificity = 97.6%). There was no correlation between WBC, NEUT%, NLR, and the occurrence of DSWI.ConclusionsFor patients who underwent sternotomy, CRP levels from the 10th postoperative day were correlated with the occurrence of DSWI. Early diagnosis of DSWI using CRP may be effective and can be used as a focused indicator to detect the presence of DSWI in patients as early as possible.
Sweat testing and cystic fibrosis - Test performance before and after a quality improvement project in a South African tertiary hospital laboratory.
Zama A, Zemlin AE, Korf M
Ann Clin Biochem · 2026 Jan · PMID 40497297 · Publisher ↗
BackgroundThe diagnosis of cystic fibrosis (CF) is challenging due to high quantity not sufficient (QNS) rates of sweat tests, leading to frequent retesting, increasing costs and adverse impacts on patient care. This stu...
BackgroundThe diagnosis of cystic fibrosis (CF) is challenging due to high quantity not sufficient (QNS) rates of sweat tests, leading to frequent retesting, increasing costs and adverse impacts on patient care. This study aimed to assess sweat test performance and implement a quality improvement project (QIP) to reduce QNS rates.MethodsA two-part retrospective audit was conducted. Part one spanned 2 years reviewing the two-tiered testing with sweat conductivity as a screening tool, followed by chloride testing. Part two evaluated the QNS rates over two 6-month periods, separated by a QIP, which involved technologist training, clinician education, patient preparation protocols and revised testing procedures.ResultsOver the 2-year period, 425 sweat tests were performed on 291 patients. Sweat conductivity testing demonstrated a lower QNS rate, 13% (31/238), compared to sweat chloride testing's 31% (33/105). High QNS rates were observed in younger infants and in malnourished or acutely ill patients. Post-QIP, the QNS rates for the total study population decreased by 5%, from an initial 30% to 25% in the sweat chloride cohort, while the acceptable QNS rate of 12% remained unchanged in the sweat conductivity cohort.ConclusionAchieving target QNS rates remains challenging, especially in younger infants, with improved QNS rates in older infants and children. Recommendations include limiting sweat testing to experienced technologists and ensuring patient readiness.
Application of the six sigma model to evaluate the analytical performance of serum lipid analytes and design quality control strategies: A multi-centre study.
Liu Q, Lin Y, Yang F … +5 more , Dai Y, Hang H, Wang M, Hu M, Yang F
Ann Clin Biochem · 2026 Jan · PMID 40497296 · Publisher ↗
BackgroundThe six sigma model is widely used in laboratory quality management. For the first time, this study introduced total allowable error (TEa) from WS/T403-2024 and 'desirable' biological variation (BV) as dual qua...
BackgroundThe six sigma model is widely used in laboratory quality management. For the first time, this study introduced total allowable error (TEa) from WS/T403-2024 and 'desirable' biological variation (BV) as dual quality goals to evaluate serum lipid analytes in six laboratories and develop individualized quality control (QC) strategies.MethodsWe collected internal quality control (IQC) and external quality assessment (EQA) data to calculate sigma values for each serum lipid analyte. Normalized sigma method decision charts were employed, and the Westgard sigma rule flow chart with batch size plus the quality goal index (QGI) guided individualized QC strategies and improvement plans.ResultsUnder the same quality goal, different QC concentrations produced varying sigma values. Sigma values also differed significantly between the two quality goals. When WS/T403-2024 was applied, all analytes except triglycerides (TGs) showed lower sigma values than under 'desirable' BV. Normalized sigma method decision charts effectively highlighted these differences. Based on the Westgard sigma rule flow chart with batch size and QGI, individualized QC strategies were created, and priority improvement measures were proposed for analytes with sigma values below six.ConclusionsThe six sigma model is a valuable tool for laboratory quality management, guiding laboratories to enhance the detection capabilities of serum lipid analytes through targeted QC strategies and improvement measures.
Detection of urinary SERPINA4 by electrochemiluminescence immunoassay and development of a diagnostic model for diabetic nephropathy.
Yang L, Li H, Chen F … +5 more , Zhang H, Wang F, Guo W, Shen Y, Liu Z
Ann Clin Biochem · 2026 Jan · PMID 40497287 · Publisher ↗
Background and objectivesSERPINA4 has been identified as a potential diagnostic biomarker for diabetic nephropathy (DN) in our previous research. This study aims to develop electrochemiluminescence immunoassay (ECLIA) me...
Background and objectivesSERPINA4 has been identified as a potential diagnostic biomarker for diabetic nephropathy (DN) in our previous research. This study aims to develop electrochemiluminescence immunoassay (ECLIA) methods for the detection of SERPINA4 and to establish a diagnostic model that incorporates additional indicators for DN.Materials and methodsAntibodies utilized in the ECLIA for the detection of SERPINA4 were labelled with ruthenium and biotin, respectively. The reliability of ECLIA was evaluated based on its linear range, precision, and hook effect. A total of 28 indicators were collected from 98 patients, including SERPINA4/UCr, diabetic retinopathy (DR), and duration of diabetes mellitus. A diagnostic model was developed employing Random Forest, Support Vector Machine (SVM), and Naive Bayes algorithms. The performance of the model was assessed using metrics such as area under the curve (AUC), precision, recall, and F1 score; ultimately selecting the best-performing model for final diagnosis.ResultThe ECLIA method established in this study for urinary SERPINA4 demonstrates a linearity range from 7.5 ng/mL to 16,000 ng/mL, with within-run precision (CV%) values of 0.25% and 3.78%. The diagnostic model developed using random forest exhibits optimal performance, achieving an AUC of 0.89, accuracy of 90%, sensitivity of 100%, and specificity of 70%. The top five variables ranked by importance are serum creatinine, microalbumin, SERPINA4/UCr ratio, systolic blood pressure, and total urine protein.ConclusionA method for the detection of urinary SERPINA4 using ECLIA has been successfully established. The combination of SERPINA4/UCr with other clinical indicators demonstrated strong performance in the diagnostic model developed through the random forest algorithm.
Is there utility in testing IgA-endomysial antibodies in patients with weak-positive or equivocal IgA-tissue transglutaminase antibodies in the diagnosis of coeliac disease? A critique of current NICE guidance (NG20).
Brown SD, Hitchins J, Wong NA … +4 more , Hayes A, Ogden A, Heaps A, Bright P
Ann Clin Biochem · 2026 Jan · PMID 40495807 · Publisher ↗
BackgroundCurrent coeliac disease (CD) NICE guidelines recommend testing IgA-endomysial antibodies (EMA) following a weak-positive IgA-tissue transglutaminase antibody (tTGA). Outside of patients with very high IgA-tTGA...
BackgroundCurrent coeliac disease (CD) NICE guidelines recommend testing IgA-endomysial antibodies (EMA) following a weak-positive IgA-tissue transglutaminase antibody (tTGA). Outside of patients with very high IgA-tTGA results, a positive IgA-EMA necessitates duodenal biopsy to confirm CD diagnosis, meaning a positive IgA-EMA does not alter the diagnostic pathway. Therefore, to be helpful, a negative IgA-EMA needs to reliably exclude CD.ObjectivesWe aimed to evaluate the negative predictive value (NPV) of IgA-EMA, following a weak-positive/positive IgA-tTGA, and to evaluate whether IgA-EMA result (positive or negative) affects duodenal biopsy rates.MethodsRetrospective patient cohort ( = 963) study of patients with IgA-EMA and IgA-tTGA testing, with or without evidence of duodenal biopsy. The NPV of IgA-EMA was assessed by comparison to duodenal biopsy. Duodenal biopsy rates were compared between patients with a positive/negative IgA-EMA (after positive/weak-positive IgA-tTGA).ResultsThe NPVs for CD of a negative IgA-EMA, in the context of a weak-positive or positive IgA-tTGA, were 41% and 0%, respectively ( = 45). There was a significant reduction in the proportion of patients who had a duodenal biopsy with a negative IgA-EMA (9.4%) compared to patients with a positive IgA-EMA (28.5%), following a positive/weak-positive IgA-tTGA ( = 963).ConclusionIgA-EMA does not reliably exclude CD following a positive/weak-positive IgA-tTGA result. Our data indicates that clinicians are utilizing a negative IgA-EMA, following a positive/weak-positive IgA-tTGA result, to inappropriately exclude CD. We recommend IgA-EMA be exclusively used in the context of a 'non-biopsy' approach to CD diagnosis, following a high positive IgA-tTGA, and that a negative IgA-EMA result should not be used to exclude CD in the context of a weak-positive/positive IgA-tTGA.
Effect of pH on stability and solid phase extraction of urinary free metadrenaline measurement by liquid chromatography tandem mass spectrometry.
McDonald L, Livie C, Smith K … +1 more , Johnston S
Ann Clin Biochem · 2025 Nov · PMID 40301723 · Publisher ↗
BackgroundMeasurement of urine free metadrenalines offers potential diagnostic and practical advantages over urinary fractionated metadrenalines in detection of phaeochromocytoma and paraganglioma, including sample colle...
BackgroundMeasurement of urine free metadrenalines offers potential diagnostic and practical advantages over urinary fractionated metadrenalines in detection of phaeochromocytoma and paraganglioma, including sample collection without acid preservative. Here, we evaluate stability with and without sample acidification as well as pH implications for analysis by solid-phase extraction (SPE) and liquid chromatography tandem mass spectrometry.MethodsSpot urine samples were adjusted to pH 3 or unacidified on day of collection and stored at room temperature, 4°C or -20°C, for up to 28 days to assess changes in free metadrenaline concentrations over time. Extraction of unacidified versus acidified urine was examined by comparing peak areas and measuring concentrations present in sample eluents according to two SPE methodologies.ResultsFree metadrenalines remained stable in urine with or without acidification for up to 28 days, with mean reduction in concentrations of <10% for all storage conditions. Measured concentrations progressively increased without acidification at room temperature at low concentrations but remained constant when spiked with pathological concentrations. Peak areas were up to 97-fold lower in acidified than unacidified samples when extracted using weak cation exchange (WCX). On average 64% of analyte eluted in the flowthrough in acidified samples relative to 1.5% without acidification. By contrast, over 99% was retained in the extract using polar extraction at either pH.ConclusionUrine free metadrenalines remain stable at room temperature for up to 28 days and are more efficiently extracted without use of acid preservative if using WCX methodology.
Pseudohyperphosphatemia induced by endogenous lipoproteins: New elements supporting an interference with ammonium phosphomolybdate-based methods.
Lefèvre CR, Le Divenah F, Paterek B … +6 more , Cankaya K, Ropert-Bouchet M, Letourneux E, Pawlowski M, Collet N, Bendavid C
Ann Clin Biochem · 2025 Nov · PMID 40301702 · Publisher ↗
BackgroundInorganic phosphate (Pi) is a crucial electrolyte for maintaining homeostasis. Most methods measure Pi using ammonium phosphomolybdate under highly acidic conditions. Phospholipid-rich substances, such as lipos...
BackgroundInorganic phosphate (Pi) is a crucial electrolyte for maintaining homeostasis. Most methods measure Pi using ammonium phosphomolybdate under highly acidic conditions. Phospholipid-rich substances, such as liposomal amphotericin B, have been previously reported to artificially elevate Pi levels due to phospholipid hydrolysis in the acidic medium. This study aimed to investigate whether endogenous lipoproteins interfere with Pi measurement in cases of hyperlipidemia.MethodsWe conducted a retrospective study comparing mean Pi levels in 194,636 patients divided in groups with varying degrees of lipemia. Additionally, we performed a prospective study involving 85 patients presenting a range of lipemia to evaluate changes in Pi levels before and after plasma high-speed centrifugation-filtration, which retains all endogenous lipoproteins.ResultsThe retrospective study revealed a significant increase in Pi levels in relation with the degree of lipemia ( < .0001). The prospective study demonstrated a significant decrease in phosphatemia ( < .0001), with mean Pi levels of 1.36 mmol/L (4.22 mg/dL) before filtration and 1.27 mmol/L (3.94 mg/dL) after filtration, representing a mean decrease of 6.8%. Furthermore, the bias, defined as 100*(([Pi] - [Pi])/[Pi]), was correlated with the lipemia level (r = 0.34, = .001).ConclusionsThis study confirms that hyperlipidemia induces an analytically significant pseudohyperphosphatemia in a lipemia-dependent manner.
Investigating the effect of icterus interference on a creatinine Roche enzymatic methodology.
Spencer KS, Duvall LE
Ann Clin Biochem · 2025 Nov · PMID 40220018 · Publisher ↗
BackgroundIt is well established that high bilirubin concentrations can lead to erroneous creatinine results when measured by a Jaffe-based method. However, the effects of bilirubin on enzymatic methods appear less well-...
BackgroundIt is well established that high bilirubin concentrations can lead to erroneous creatinine results when measured by a Jaffe-based method. However, the effects of bilirubin on enzymatic methods appear less well-defined. The Roche Cobas 8000 enzymatic creatinine (CREP2) has an unconjugated bilirubin icterus limit of 20 mg/dL, equivalent to a bilirubin concentration of 342 µmol/L. Many hepatology patients have bilirubin levels much higher than this limit, and laboratories are unable to release creatinine results on these complex patients. This is particularly challenging for patient management, as creatinine is a key test and is a prerequisite for many procedures, imaging studies and treatments.MethodsTwo spiking studies were carried out, the first to define the interference effect of bilirubin on enzymatic creatinine measurement, and the second to see if this interference could be mitigated via dilution. Serum samples ( = 50) were spiked with a concentrated bilirubin solution. Indices, bilirubin and creatinine were measured using the Roche Cobas 8000 c702 automated analyser according to manufacturer instructions.ResultsThe spiking study found a negative linear relationship and as bilirubin concentrations increased, the measured creatinine concentration decreased (R = 0.7828, y = -0.0597x + 15.603). Samples with a bilirubin concentration over 246 µmol/L demonstrated an average 1.48% drop in creatinine concentration per 25 µmol/L increase in bilirubin.ConclusionsA service improvement was applied where creatinine results can be released on samples with a bilirubin concentration up to 550 µmol/L, with an appropriate comment, upon request by the clinician.
The effect of inadequate drying of blood spots on newborn screening analyte concentrations.
Moat SJ, Levi M, Birch M … +6 more , Worlock N, Sundas C, Woodcock L, Kay J, de Souza S, Rodham A
Ann Clin Biochem · 2025 Nov · PMID 40220017 · Publisher ↗
BackgroundA critical pre-analytical phase of newborn screening (NBS) testing involves the drying of blood applied to the blood collection devices to form the dried blood spots (DBS). Guidance states that blood applied sh...
BackgroundA critical pre-analytical phase of newborn screening (NBS) testing involves the drying of blood applied to the blood collection devices to form the dried blood spots (DBS). Guidance states that blood applied should be air-dried for a minimum of 3 h. A recent survey highlighted that a number of DBS specimens routinely received into laboratories have a 'crinkled' appearance and that DBS specimens collected in a hospital setting are transported to the laboratory in sealed plastic bags. To date no scientific studies have evaluated aspects of blood drying on DBS NBS analyte concentrations.MethodsWe undertook experiments to recreate 'crinkled' DBS specimens in the laboratory and assess the impact on analyte concentrations. We also assessed the impact of storing collection devices following blood application in hermetically sealed plastic bags to impede the drying process. Experiments were performed using whole blood enriched with thyroid stimulating hormone, immunoreactive trypsinogen, phenylalanine, tyrosine, leucine, methionine, octanoyl-carnitine, decanoyl-carnitine, isovaleryl-carnitine and glutaryl-carnitine to pathophysiological concentrations.Results'Crinkled' DBS specimens produced significantly lower results (mean -15.5%, range -25.1 to -4.7%) for all analytes measured versus air-dried DBS specimens ( < .05). Analyte concentrations obtained from DBS specimens following storage in plastic bags before drying were significantly lower (mean -41.6%, range -60.0 to -27.6%) for all analytes measured ( < .05) versus air-dried DBS specimens.ConclusionResults from this study demonstrate that all DBS specimens with a crinkled appearance and those received in plastic specimen bags should be rejected and a repeat specimen collected to prevent erroneous screening results.
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