Clinical biochemistry最新文献

{"title":"Plasma lipase and hemolysis on Roche Cobas c503 analysers: No evidence of the need to lower the interference threshold","authors":"Denis Monneret","doi":"10.1016/j.clinbiochem.2025.111022","DOIUrl":"10.1016/j.clinbiochem.2025.111022","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111022"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine proteome uncovers common mechanisms between mucopolysaccharidosis types I and II","authors":"Xiaozhou Yuan ,&nbsp;Donghao Jia ,&nbsp;Gefan Wan ,&nbsp;Chengbin Wang ,&nbsp;Kefu Liu ,&nbsp;Yan Meng ,&nbsp;Jinyan Duan","doi":"10.1016/j.clinbiochem.2025.111011","DOIUrl":"10.1016/j.clinbiochem.2025.111011","url":null,"abstract":"<div><h3>Background and aims</h3><div>Mucopolysaccharidosis (MPS) types I and II are two types of rare lysosomal storage diseases, which lead to the accumulation of glycosaminoglycans due to the lack of the enzyme alpha-L-iduronidase and iduronate 2-sulfatase respectively. There are some similar pathogenic mechanisms and clinical phenotypes but also some specific minute manifestations between these two subtypes.</div></div><div><h3>Materials and methods</h3><div>We used tandem mass tag mass spectrometry to analyze the differential protein profiles in the urine of MPS I and MPS II patients, and then used parallel reaction monitoring (PRM) to verify our results. We detected the differentially expressed proteins (DEPs) of MPS I and MPS II compared with the control group separately.</div></div><div><h3>Results</h3><div>We focused on 227 DEPs which showed consistent changes in the urine of both MPS I and MPS II. PRM analysis verified that up-regulated hexosaminidase B and down-regulated hemoglobin alpha-1 showed significant difference in the urine of both subtypes. In addition, we found 391 DEPs by comparative analysis of MPS I and MPS II proteomes and found that DHRS2 contributed to the difference between the two subtypes by PRM verification.</div></div><div><h3>Conclusion</h3><div>We found that the urine of the two subtypes showed up-regulated HEXB and down regulated HBA1, while DHRS2 was significantly different in the urine of the two subtypes.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111011"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “CA19-9, CEA and PIVKA-II as a novel panel of serum markers for diagnosis of pancreatic cancer” [Clin. Biochem. 137 (2025) 110902]","authors":"Meifang Wang ,&nbsp;Hongying Bu ,&nbsp;Weijia Luo ,&nbsp;Xi Zeng ,&nbsp;Guodong Chen ,&nbsp;Yingchun He ,&nbsp;Deliang Cao","doi":"10.1016/j.clinbiochem.2025.111017","DOIUrl":"10.1016/j.clinbiochem.2025.111017","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111017"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical relevance of the Maglumi immunoassay for anti-GAD65 in diabetes and neurological disorders: Analytical challenges and diagnostic insights","authors":"Gonzalo Verdú ,&nbsp;Antonio Jesús Blanco-Carrasco ,&nbsp;Raquel Ruiz-García ,&nbsp;Albert Saiz ,&nbsp;Manuel Morales-Ruiz ,&nbsp;Gregori Casals","doi":"10.1016/j.clinbiochem.2025.111024","DOIUrl":"10.1016/j.clinbiochem.2025.111024","url":null,"abstract":"<div><h3>Introduction</h3><div>Anti-GAD65 is an established diagnostic biomarker for autoimmune diabetes and neurological syndromes associated with GAD antibody-spectrum disorders. Automated chemiluminescence-based immunoassays such as Maglumi are increasingly used, but their behavior at high antibody concentrations remains poorly characterized. We report the analytical concordance between Maglumi and radioimmunoassay (RIA), the cut-off titer that differentiates neurological from diabetic patients, and the hook effect of the immunoassay.</div></div><div><h3>Materials and methods</h3><div>Anti-GAD65 levels were analyzed in samples from 90 patients with suspected autoimmune diabetes or neurological syndromes, using Maglumi 2000® and RIA (Medipan®). Analytical concordance was assessed by Passing–Bablok regression, Bland–Altman plots, and Cohen’s kappa. ROC curve analysis identified diagnostic thresholds, and dilution studies were performed in samples with unexpectedly low values to assess a potential hook effect.</div></div><div><h3>Results</h3><div>Maglumi results were approximately five times higher than RIA results (slope = 5.364; R² = 0.908); agreement was higher in endocrine (R² = 0.998) than in neurological patients (R² = 0.891). A cutoff of 6778 IU/mL discriminated neurological patients from diabetic patients (AUC = 0.96). Sixteen samples showed a hook effect, with direct (undiluted) values ≤273 IU/mL, while the corrected titers after dilution exceeded 20,000 IU/mL. A linear regression confirmed an inverse relationship between direct and true titers (r = –0.79, p &lt; 0.05).</div></div><div><h3>Discussion</h3><div>Maglumi anti-GAD65 immunoassay provides reliable discrimination between endocrine and neurological patients but requires method-specific cutoffs to avoid misclassification. Hook effect was frequent in high-titer neurological samples, potentially leading to misdiagnosis, underscoring the need for routine dilution protocols to improve diagnostic reliability.</div></div><div><h3>Conclusions</h3><div>Standardized dilution protocols and appropriate cutoffs are essential to ensure reliable anti-GAD65 testing with Maglumi chemiluminescent immunoassay, particularly in neurological indications.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111024"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the interference: How therapeutic monoclonal antibodies challenge serum protein electrophoresis and immunofixation","authors":"Julie Milandri ,&nbsp;Marine Jaillard ,&nbsp;Mariette Laffineur ,&nbsp;Magali Dechomet ,&nbsp;Marie N. Kolopp-Sarda","doi":"10.1016/j.clinbiochem.2025.111038","DOIUrl":"10.1016/j.clinbiochem.2025.111038","url":null,"abstract":"<div><h3>Introduction</h3><div>Serum protein electrophoresis and immunofixation electrophoresis are routinely used to diagnose and monitor monoclonal gammopathies. However, several therapeutic monoclonal antibodies are detectable by these techniques and may mimic a pathological monoclonal protein, leading to diagnostic confusion. This study aimed to evaluate potential interferences caused by these treatments and to characterize their electrophoretic migration profiles and detection thresholds.</div></div><div><h3>Materials and methods</h3><div>Seven therapeutic monoclonal antibodies (daratumumab, isatuximab, rituximab, elranatamab, teclistamab, eculizumab, and ravulizumab) were assessed using an overloaded hypogammaglobulinemic serum model. Each antibody was tested at seven decreasing concentrations, from one point five grams per liter to zero point one gram per liter. All dilutions were analyzed by capillary electrophoresis and immunofixation electrophoresis.</div></div><div><h3>Results</h3><div>Validation was performed using daratumumab, for which interference is well documented. Rituximab and elranatamab consistently generated a discrete peak in the slow-gamma region on serum protein electrophoresis, associated with an IgG kappa band on immunofixation electrophoresis. Teclistamab migrated in the mid-gamma region and produced an IgG lambda band, detectable down to zero point fifteen gram per liter on serum protein electrophoresis and zero point zero two gram per liter on immunofixation electrophoresis. Ravulizumab, an IgG kappa antibody migrating in the beta-two region, remained detectable down to zero point five gram per liter and zero point one gram per liter, respectively.</div></div><div><h3>Conclusions</h3><div>This work specifies the electrophoretic behavior of several monoclonal antibody therapies, helping distinguish therapy-related peaks from true monoclonal gammopathy. These findings support the systematic use of confirmatory strategies—particularly reflex immunofixation—to ensure accurate interpretation of electrophoresis results in patients receiving monoclonal antibody treatment.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111038"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biological diagnosis of Alzheimer’s disease using blood-based biomarkers: a Canadian prospective","authors":"Pankaj Kumar,&nbsp;Ali Mousavi,&nbsp;Hans Frykman","doi":"10.1016/j.clinbiochem.2025.111015","DOIUrl":"10.1016/j.clinbiochem.2025.111015","url":null,"abstract":"<div><div>Dementia is the most common type of neurodegenerative disease, with Alzheimer’s Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential for mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The cerebrospinal fluid Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discuss the biological configuration and normal function of involved proteomics in AD including Aβ and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review blood-based biomarkers’ analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111015"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A panel (CA19-9, CEA and PIVKA-II) of serum markers for pancreatic cancer diagnosis","authors":"Guo-Ming Zhang","doi":"10.1016/j.clinbiochem.2025.111025","DOIUrl":"10.1016/j.clinbiochem.2025.111025","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111025"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calculated small-dense and large-buoyant low-density lipoprotein-cholesterol and their ratio in predicting coronary artery disease risk: A cohort study in Thailand","authors":"Thanyatorn Chantivas ,&nbsp;Prin Vathesatogkit ,&nbsp;Anchalee Chittamma ,&nbsp;Nisakron Thongmung ,&nbsp;Martin H Kroll ,&nbsp;Pornpen Srisawasdi","doi":"10.1016/j.clinbiochem.2025.111018","DOIUrl":"10.1016/j.clinbiochem.2025.111018","url":null,"abstract":"<div><h3>Objectives</h3><div>Calculated, small dense low-density lipoprotein cholesterol (CsdLDL-C), derived using the Sampson equation, has been proposed as a screening tool for atherosclerotic cardiovascular disease risk. The current study investigated the utility of CsdLDL-C and calculated large buoyant low-density lipoprotein cholesterol (ClbLDL-C) for coronary artery disease (CAD) risk assessment in a Thai population.</div></div><div><h3>Methods</h3><div>This study included 6448 participants without prior CAD from the Electricity Generating Authority of Thailand (EGAT) prospective cohort (2007–2009). CsdLDL-C and ClbLDL-C were estimated from standard lipid panel measurements. Associations with CAD risk were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>Over a mean follow-up period of 10.24 ± 1.01 years, 262 (4.06 %) participants experienced CAD events. At the optimal cutoffs, high CsdLDL-C [&gt;1.08 mmol/L (41.85 mg/dL)] was significantly associated with incident CAD events (HR = 1.57; 95 % CI = 1.22–2.02), whereas high ClbLDL-C [&gt;2.52 mmol/L (97.59 mg/dL)] was inversely associated with incident CAD events (HR = 0.72; 95 % CI = 0.56-0.92). The CsdLDL-C/ClbLDL-C ratio exhibited the strongest association (HR = 2.02; 95 % CI = 1.58–2.60) among all lipid parameters. When individually added to the pooled cohort risk equation, CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio remained significant predictors of new-onset CAD. They also demonstrated good discriminatory power (<em>P</em> &lt; 0.004).</div></div><div><h3>Conclusion</h3><div>CsdLDL-C and ClbLDL-C, derived using the Sampson equation, were significantly associated with CAD risk in the opposite direction. Their ratio had greater predictive effectiveness. Incorporating CsdLDL-C and the CsdLDL-C/ClbLDL-C ratio into cardiovascular risk assessment models may improve early identification of at-risk individuals.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111018"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliable LC-MS/MS method development and validation for the determination of methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine in dried blood spots","authors":"Chunyan Zhang ,&nbsp;Nan Bai ,&nbsp;Yanling Yang ,&nbsp;Yuxuan Cheng ,&nbsp;Xiyu He ,&nbsp;Meng Wang ,&nbsp;Honghui Zhou ,&nbsp;Yaping Tian","doi":"10.1016/j.clinbiochem.2025.111013","DOIUrl":"10.1016/j.clinbiochem.2025.111013","url":null,"abstract":"<div><h3>Objectives</h3><div>Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantify methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine associated with metabolic disorders.</div></div><div><h3>Design and methods</h3><div>According to Clinical Laboratory Standards Institute (CLSI) guidelines, various analytical performances (i.e., precision, linearity, accuracy and reference intervals) were rigorously evaluated. Meanwhile, sample preparation, chromatographic separation and mass spectrometric detection and incorporating stable isotope-labeled internal standards were optimized. Furthermore, calibrators and quality controls were developed to ensure standardization and traceability.</div></div><div><h3>Results</h3><div>The coefficient of variations for precision were less than 10.0 %. Meanwhile, the results showed high accuracy (recoveries: 94.57 %–109.60 %) and robust linearity (R² &gt; 0.9935) over clinically relevant ranges. The limits of detection and limits of quantification for all analytes were established, enabling sensitive detection of pathological elevations. Reference intervals for pediatric populations (ages 0–1 month and 2 months to 18 years) were determined, providing essential baselines for clinical interpretation.</div></div><div><h3>Conclusions</h3><div>The newly developed method demonstrated good analytical performance and offers a standardized, high-throughput solution for clinical laboratories to improve early diagnosis and personalized management of metabolic diseases.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111013"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical implementation and outcome evaluation of dihydropyrimidine dehydrogenase (DPYD) pharmacogenomic testing for fluoropyrimidine dosing in a Canadian Provincial Healthcare center","authors":"Fang Wu ,&nbsp;Song Lu ,&nbsp;Dan Zhang ,&nbsp;Nelly Abdelfatah ,&nbsp;Vijayananda Kundapur ,&nbsp;Fergall Magee ,&nbsp;Yanwei Xi","doi":"10.1016/j.clinbiochem.2025.111008","DOIUrl":"10.1016/j.clinbiochem.2025.111008","url":null,"abstract":"<div><h3>Background</h3><div>5-Fluorouracil (5-FU) and its pro-drug, capecitabine, are widely used to treat solid tumors. Patients with dihydropyrimidine dehydrogenase (<em>DPYD</em>) deficiency are at increased risk for severe treatment-related toxicity. This study reported the implementation of <em>DPYD</em> genotyping in clinical practice and assessed the impact of genotype-guided dosing on clinical outcomes.</div></div><div><h3>Methods</h3><div>An in-house pharmacogenomic testing using the Elucigene <em>DPYD</em> genotyping kit (Yourgene Health, UK) was established to detect the four most common clinically actionable <em>DPYD</em> alleles, including <em>*2A, *13, HapB3</em> and c.2846A&gt;T (rs67376798). Six months post-implementation, a retrospective chart review assessed genotype results, chemotherapy regimens, dose modifications, adverse events related to 5-FU or capecitabine, and demographics. Data were de-identified for analysis.</div></div><div><h3>Results</h3><div>Analytical validation of the <em>DPYD</em> assay showed 100 % sensitivity, specificity, accuracy, reproducibility, and repeatability. The genotyping workflow was successfully integrated into clinical practice, with a rapid turnaround time to meet oncology treatment planning. From July to December 2024, 299 patients underwent <em>DPYD</em> testing; variants were identified in 22 patients, including 20 patients (6.7 %) with clinically significant variants conferring a reduced DPD function and 2 patients with a variant (c.483 + 18G&gt;A; rs56276561) that retains normal DPD function. Among those variants, <em>HapB3</em> (n = 18) was the most frequent one, characterized by c.1129-5923C&gt;G and c.1236G&gt;A <em>(</em>rs75017182, rs56038477) co-occurring with c.483 + 18G&gt;A (rs56276561). Of 233 patients receiving 5-FU-based chemotherapy, 13 were variant carriers. Genotype-guided dosing allowed early dose optimization, and all carriers completed at least three treatment cycles, with one severe adverse event attributed to oxaliplatin rather than 5-FU.</div></div><div><h3>Conclusions</h3><div>This study reported the integration of <em>DPYD</em> pharmacogenomic testing into oncology care and evaluated the post-implementation clinical outcomes, highlighting the critical role of pharmacogenomic testing in optimizing cancer treatment and improving patient safety.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111008"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}