Clinica Chimica Acta最新文献

{"title":"Optimized NMDAR autoantibody detection via combined NR1-4a LCBA and NR1/NR2 fusion FCBA","authors":"Baoming He ,&nbsp;Jing Gan ,&nbsp;Junjuan Mao ,&nbsp;Xiao Wang ,&nbsp;Dong Yang ,&nbsp;Tong Peng ,&nbsp;Jianlin Liu ,&nbsp;Xinying Jing ,&nbsp;Li Meng ,&nbsp;Quekun Peng","doi":"10.1016/j.cca.2026.120834","DOIUrl":"10.1016/j.cca.2026.120834","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune encephalitis (AE) is a group of neurological disorders mediated by autoantibodies targeting proteins within the central nervous system, of which anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor (NMDAR) encephalitis is the most common. The current Cell-Based Assay (CBA) that is primarily used to detect NMDAR antibodies in clinical settings, however, exhibits several limitations, including both false-positive and false-negative results. The aim of this research is to improve the sensitivity and specificity of NMDAR antibody detection through optimization of the CBA detection model.</div></div><div><h3>Methods</h3><div>In this research, recombinant vectors were constructed to express full-length, truncated, and fusion proteins of NMDA Receptor Subunit 1 (NR1) or/and NMDA Receptor Subunit 2B (NR2B). Six distinct models for CBA detection (Model I-Model VI) were established via transfection into CHO cells. A total of 36 serum (SER) and cerebrospinal fluid (CSF) samples from 18 anti-NMDAR patients were analyzed alongside 30 SER and CSF samples from individuals with other neurological disorders and 20 SER samples from healthy controls to systematically evaluate the detection efficacy across each model.</div></div><div><h3>Results</h3><div>The findings indicate that the Model IV (NR1-4a single subunit) exhibited optimal diagnostic sensitivity(true positive identified) at 100% by live cell-based assay (L-CBA). In contrast, Model V (NR1–1a Amino Terminal Domain (ATD) fused with NR2B ATD) displayed the highest technical sensitivity(titer detection limit) by the fixed cell-based assay (F-CBA), which was significantly superior to the other models (<em>P</em> <em>&lt;</em> 0.05). The combined testing of Models IV and V resulted in a substantial enhancement of the overall performance of the assay. Specifically, the sample diagnostic sensitivity of the SER increased from 83.3% of traditional detection method(Model I) to 100% and the technical sensitivity was improved with highly significant difference to Model I(SER: <em>P</em> <em>&lt;</em> 0.0001; CSF: <em>P</em> <em>&lt;</em> 0.05).</div></div><div><h3>Conclusion</h3><div>The combined detection established in this research markedly improved both accuracy and reliability in NMDAR antibody detection, effectively addressing the limitations associated with traditional detection methods. This optimized detection provides a robust foundation for early diagnosis and therapeutic intervention in cases of NMDAR encephalitis, thereby enhancing patient prognosis.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120834"},"PeriodicalIF":2.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948484","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":"Expansion of CKD diagnostics through biosensor technology: An early detection approach","authors":"Ganesh Pd Sahu,&nbsp;Aniket Nandi,&nbsp;Atanu Saha,&nbsp;Swagnik Chakraborty,&nbsp;S.S. Ganti,&nbsp;Kalicharan Sharma","doi":"10.1016/j.cca.2026.120833","DOIUrl":"10.1016/j.cca.2026.120833","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a complicated global health disease that causes serious health issues like kidney failure and heart-related problems. These complications make the conditions worse for the patients and also increase the mortality rate globally, which is 41.5% since 1990. Most individuals are not aware that they have renal disease until it is highly advanced because it doesn't show any symptoms in its early stages. The prevalence of CKD is higher than average, and replacement therapy is required for the majority of individuals who have reached stage 5. Various diagnostic techniques have been developed for the detection of CKD, but they are not user-friendly and are much costlier. Therefore, the early detection of CKD through biosensor-based techniques has been used to decrease the overall burden to prevent patients from developing serious renal problems. The emergence of biosensors is one of the most promising solutions, offering a cost-effective and precise method for the early detection of various diseases. In this review, we have systematically compiled the current data since the last ten years (2015–2025), complications, traditional vs modern techniques, recent biomarkers and biosensor-based techniques, which include various classes of biosensors, including electrochemical, optical, fluorescent/colorimetric, and AI-assisted biosensors.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120833"},"PeriodicalIF":2.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948489","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":"C-peptide in polycystic ovary syndrome","authors":"Faezeh Mahd Gharebagh ,&nbsp;Sana Najafi ,&nbsp;Asra Zeinalpour ,&nbsp;Rozhina Sadat Pirouzmand ,&nbsp;Hojat Ghasemnejad-Berenji ,&nbsp;Mortaza Taheri-Anganeh","doi":"10.1016/j.cca.2026.120829","DOIUrl":"10.1016/j.cca.2026.120829","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age, characterized by irregular menstruation, hyperandrogenism, and the presence of ovarian cysts. The fundamental pathophysiology is intricate, encompassing insulin resistance, hyperinsulinemia, and impaired hormonal control. C-peptide, a consequence of insulin production, has emerged as a valuable biomarker for evaluating insulin resistance and beta-cell functionality in PCOS. Although previously deemed biologically inactive, current research indicates that C-peptide actively participates in cellular signaling, initiating pathways such as calcium-dependent signaling and endothelial nitric oxide synthase. Increased C-peptide levels in PCOS signify hyperinsulinemia and insulin resistance, which exacerbate the syndrome's metabolic and reproductive disorders. Clinical data substantiates the utilization of C-peptide as a diagnostic instrument, especially in assessing insulin resistance in non-obese PCOS patients, where conventional metrics such as body mass index (BMI) may be inapplicable. Nonetheless, obstacles persist in the standardization of C-peptide testing methodologies, and its interpretation may be affected by extrinsic factors like pharmaceutical interventions or concomitant conditions like obesity and diabetes. Individualized diagnostic methods are necessary due to the phenotypic variability of PCOS, which results in varying C-peptide levels among distinct subtypes. Future research must concentrate on enhancing diagnostic procedures, investigating the significance of C-peptide in the long-term management of PCOS, and elucidating its potential as a predictive biomarker for associated metabolic disorders. This review emphasizes the necessity for additional investigations of C-peptide in clinical practice to enhance diagnostic and therapeutic approaches for PCOS.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120829"},"PeriodicalIF":2.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939301","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":"Circulating suPAR as a noninvasive biomarker of fibrosis and immune activation in autoimmune liver diseases","authors":"Fuguo Zhan ,&nbsp;Tianbin Chen ,&nbsp;Jun Liang ,&nbsp;Can Liu ,&nbsp;Mingdong Huang ,&nbsp;Longguang Jiang","doi":"10.1016/j.cca.2026.120831","DOIUrl":"10.1016/j.cca.2026.120831","url":null,"abstract":"<div><h3>Aim</h3><div>Noninvasive assessment of fibrosis in autoimmune liver diseases (AILDs) remains challenging. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic immune activation, but its role in AILDs is unclear. This study aimed to evaluate the diagnostic performance of circulating suPAR in AILDs and its association with fibrosis severity and immune activation.</div></div><div><h3>Methods</h3><div>A retrospective study included 117 patients with AILDs (<em>n</em> = 61), chronic hepatitis B (CHB, <em>n</em> = 33), metabolic dysfunction-associated steatotic liver disease (MASLD, <em>n</em> = 23), and 44 healthy controls. Serum suPAR was measured by chemiluminescent immunoassay. Correlations with fibrosis indices (APRI, FIB-4), liver stiffness measurement (LSM), and IgG were assessed. ROC analysis evaluated diagnostic accuracy.</div></div><div><h3>Results</h3><div>Serum suPAR was significantly higher in AILDs than in controls, CHB, and MASLD (median 5.16 vs. 3.58, 3.92, and 3.13 ng/mL; all <em>P</em> &lt; 0.001). suPAR correlated strongly with APRI (<em>r</em> = 0.66), FIB-4 (<em>r</em> = 0.65), and LSM (<em>r</em> = 0.62), and modestly with IgG (<em>r</em> = 0.31). ROC analysis demonstrated robust discrimination between AILDs and controls (AUC = 0.839), CHB (AUC = 0.724), and MASLD (AUC = 0.944). Patients with higher suPAR levels exhibited more advanced fibrosis and greater biochemical evidence of liver injury.</div></div><div><h3>Conclusions</h3><div>Circulating suPAR is elevated in AILDs, reflecting fibrosis and immune activation. suPAR provides complementary, antibody-independent diagnostic value and may serve as a noninvasive biomarker for differentiating AILDs from CHB and MASLD in clinical practice.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"583 ","pages":"Article 120831"},"PeriodicalIF":2.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932462","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":"Circulating microRNA electrochemical assays in thyroid cancer","authors":"Muteb Alanazi ,&nbsp;Jowaher Alanazi ,&nbsp;Tareq Nafea Alharby ,&nbsp;Abdullah S. Alhamed ,&nbsp;Sameer Shaikh","doi":"10.1016/j.cca.2026.120828","DOIUrl":"10.1016/j.cca.2026.120828","url":null,"abstract":"<div><div>Thyroid cancer is the most prevalent endocrine malignancy; however, it is difficult to preoperatively distinguish between benign and malignant nodules and to ensure reliable surveillance after therapy. Circulating microRNAs (miRNAs) provide a minimally invasive molecular signal for testing, although conventional qPCR and sequencing pipeline technologies have cost, labor, and standardization challenges. This review summarizes the progress in the electrochemical biosensing of thyroid-relevant miRNAs along sample-to-clinic continuum. Signal recovery is strongly determined by preanalytical variables such as matrix selection (serum, plasma, whole blood, or extracellular vesicles), hemolysis control, storage conditions, extraction chemistry, spike-in controls, and normalization strategy using exogenous and endogenous controls. Yield can be further stabilized by the enrichment of extracellular vesicles, low-input protocols, and the reduction of batch effects. Analytically, voltammetric, impedimetric, electrochemiluminescent, and photoelectrochemical formats use rational probe design with nanostructured interfaces, such as gold nanoparticles, graphene derivatives, and MXenes, along with catalytic amplification duplex-specific nuclease (DSN), hybridization chain reaction (HCR), catalytic hairpin assembly (CHA), or CRISPR modules. While many platforms report ultra-low analytical limits of detection (femtomolar to attomolar) and wide linear ranges in buffer or spiked matrices, fewer studies have established functional sensitivity and clinical detection rates in unprocessed patient serum/plasma, where endogenous inhibitors and biological heterogeneity can dominate performance. Recurring signatures, such as miR-146b, miR-221, miR-222, and miR-21, have been shown to aid in early diagnosis, risk stratification, and postoperative follow-ups, whereas multiplex panels and cartridge-based platforms have been shown to be resilient to biological heterogeneity and complement cytology, mutation panels, and thyroglobulin, particularly in indeterminate Bethesda III or IV nodules and antibody-interfered follow-ups. The remaining limitations are inter-study method variation, poor inter-center validation, and unclear regulatory mechanisms of these miRNAs. An effective roadmap will focus on balanced collection and processing, preset thresholds with external calibration and commutable references, and blind prospective trials integrated into clinical practice with decision curve and health-economic analyses to speed up translation.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120828"},"PeriodicalIF":2.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932490","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":"Investigating the diagnostic significance of serum NRCAM in small cell lung cancer","authors":"Yinyi Chen ,&nbsp;Kexin Han ,&nbsp;Liping Wei ,&nbsp;Xinlu Sun ,&nbsp;Yanzhao Liu ,&nbsp;Qunxia Wang ,&nbsp;Yang Wu ,&nbsp;Simei Chen ,&nbsp;Jianlin Yu ,&nbsp;Yi Luo ,&nbsp;Lili Wen ,&nbsp;Liming Tan","doi":"10.1016/j.cca.2025.120815","DOIUrl":"10.1016/j.cca.2025.120815","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the clinical significance of serum neuronal cell adhesion molecule (NRCAM) in small cell lung cancer (SCLC) diagnosis.</div></div><div><h3>Methods</h3><div>Serum NRCAM levels were measured using enzyme-linked immunosorbent assay in 80 SCLC patients, 98 patients with non-small cell lung cancer (NSCLC), 73 patients with pulmonary nodules (PN) and 56 healthy controls. Neuron specific enolase (NSE) and progastrin-releasing peptide (ProGRP) expression were detected using chemiluminescence immunoassay.</div></div><div><h3>Results</h3><div>(1) Significant differences were detected in serum NRCAM, NSE and ProGRP levels among the groups (<em>P</em> &lt; 0.05), with the highest levels observed in SCLC patients. (2) Correlation assessment revealed that serum NRCAM concentrations were positively correlated with smoking (<em>r</em> = 0.39) and lymph node metastasis (<em>r</em> = 0.37) (both <em>P</em> &lt; 0.01). (3) NRCAM concentration was positively correlated with the clinical stage of SCLC, being significantly lower in stages I-II compared to stages III-IV (<em>P</em> &lt; 0.01), and was remarkably lower in the non-metastatic group of SCLC relative to the metastatic group (<em>P</em> &lt; 0.01). (4) Compared to the NSCLC group, ProGRP exhibited the largest area under the receiver operating characteristic curve (AUC) and the highest sensitivity for SCLC diagnosis, with values of 0.86 and 76 %, respectively. NRCAM had the highest specificity for SCLC diagnosis (94 %). Compared to the PN group, NRCAM exhibited a larger AUC (0.81) and higher sensitivity (74 %) for SCLC diagnosis. Conversely, NSE displayed a higher specificity for SCLC diagnosis (93 %). The combined diagnostic approach using NRCAM, NSE, and ProGRP yielded the largest AUC and the highest sensitivity, at 0.94 and 91 %, respectively. (5) Binary logistic regression analysis revealed that smoking and lymph node metastasis were potential risk factors influencing serum NRCAM levels.</div></div><div><h3>Conclusions</h3><div>NRCAM possess significant potential for diagnosing SCLC and distinguishing SCLC from NSCLC and PN. Moreover, the combination detection of NRCAM, NSE, and ProGRP may enhance diagnostic performance, offering a novel clinical strategy for SCLC.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120815"},"PeriodicalIF":2.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932493","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":"Acute kidney injury: Detection, risk stratification, and predictive biomarkers","authors":"Nazmin Bithi ,&nbsp;Earnest J.P. Daniel ,&nbsp;Sridevi Devaraj","doi":"10.1016/j.cca.2026.120830","DOIUrl":"10.1016/j.cca.2026.120830","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) is a complex multifactorial syndrome characterized by a rapid decline in kidney function, frequently observed in hospitalized and critically ill patients. Despite its high morbidity and mortality, current diagnostic criteria—based primarily on serum creatinine and urine output—are delayed and non-specific, limiting early detection and timely intervention.</div></div><div><h3>Content</h3><div>Over the past two decades, extensive research has led to the discovery and validation of a diverse array of AKI biomarkers that reflect distinct pathophysiological mechanisms, including tubular cell injury (e.g., NGAL, KIM-1), inflammation (e.g., IL-18, CCL-2 and CCL14), oxidative stress (e.g., L-FABP), cell cycle arrest (e.g., TIMP-2·IGFBP7), and endothelial dysfunction (e.g., suPAR). Additional functional biomarkers, such as urinary cystatin C and low-molecular-weight proteins like α1-microglobulin and β2-microglobulin, have emerged as sensitive indicators of proximal tubular dysfunction. These biomarkers offer promise for detecting subclinical AKI, improving risk stratification, guiding therapy, and serving as surrogate endpoints in clinical trials. However, clinical implementation remains constrained by assay variability, lack of harmonized cut-offs, cost and reimbursement barriers, and limited validation in pediatric and other specialized populations. Newer platforms, such as urinary tubular enzymes (e.g., NAG, LDH, ALP) and extracellular vehicles (EVs), continue to expand the diagnostic landscape.</div></div><div><h3>Summary</h3><div>Integration of complementary multi-marker panels with artificial intelligence–based models offers significant potential to advance precision nephrology by enabling earlier risk prediction, individualized management, and optimized clinical trial enrichment. Ongoing international standardization initiatives and multicenter validation efforts are critical to accelerating the translation of AKI biomarkers from research tools to routine clinical practice.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120830"},"PeriodicalIF":2.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932556","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":"Changing in blood cells for infection detection: “Monocyte distribution width” acts as a key determinant in differentiating localized and blood stream infections","authors":"Agostino Ognibene ,&nbsp;Maria Lorubbio ,&nbsp;Sara Montemerani ,&nbsp;Giulio Camarlinghi ,&nbsp;Tommaso Novi ,&nbsp;Claudia Artini ,&nbsp;Eva Maria Parisio ,&nbsp;Raffaella Pavani ,&nbsp;Danilo Tacconi ,&nbsp;Maurizio Zanobetti","doi":"10.1016/j.cca.2026.120819","DOIUrl":"10.1016/j.cca.2026.120819","url":null,"abstract":"<div><h3>Background</h3><div>Early identification of bloodstream infections (BSI) in the Emergency Department (ED) remains a clinical challenge. Monocyte Distribution Width (MDW), a novel biomarker available from the complete blood count, was prospectively evaluated for its diagnostic and prognostic utility in patients with suspected infection.</div></div><div><h3>Methods</h3><div>We conducted a prospective, observational cohort study enrolling 608 adult ED patients. Following a comprehensive diagnostic workup, patients were retrospectively adjudicated into three primary groups: No Infection (n = 196), Localized Infection (n = 235), and Bloodstream Infection (BSI) (n = 134). The diagnostic accuracy of MDW was compared to procalcitonin (PCT) and C-reactive protein (CRP) using receiver operating characteristic (ROC) analysis.</div></div><div><h3>Results</h3><div>In this cohort, MDW demonstrated high accuracy for BSI detection (Area Under the Curve [AUC] = 0.936), representing a statistically significant improvement over both PCT (AUC = 0.818; p &lt; 0.0001) and CRP (AUC = 0.829; p &lt; 0.0001). It also showed good accuracy in discriminating localized infections from the no-infection group (AUC = 0.748). Notably, among the biomarkers tested, MDW was the only biomarker significantly elevated in non-survivors compared to survivors (p = 0.001), indicating a unique prognostic value for in-hospital mortality.</div></div><div><h3>Conclusions</h3><div>In ED patients with suspected infection, MDW is a highly effecti<em>ve biomarker for the early dete</em>tion of BSI, demonstrating significantly higher diagnostic accuracy than PCT and CRP in this study. Its ability to help stratify patients with localized versus systemic infection and to predict mortality makes it a valuable tool for early risk assessment and clinical decision-making.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120819"},"PeriodicalIF":2.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917237","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 “Aberrantly glycosylated PSMA in urine as a potential marker for prostate cancer” [Clin. Chim. Acta 582 (2026) 120790]","authors":"Misba Khan ,&nbsp;Md. Khirul Islam ,&nbsp;Pekka Taimen ,&nbsp;Peter J. Boström ,&nbsp;Urpo Lamminmäki ,&nbsp;Janne Leivo","doi":"10.1016/j.cca.2025.120818","DOIUrl":"10.1016/j.cca.2025.120818","url":null,"abstract":"","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"581 ","pages":"Article 120818"},"PeriodicalIF":2.9,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899185","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":"Quantification of plasma mutant calreticulin for diagnosis and therapeutic response assessment of peginterferon-α in myeloproliferative neoplasms: A proof-of-concept study","authors":"Jingjing Tian ,&nbsp;Xuemei Tang ,&nbsp;Weiyan Zhou ,&nbsp;Can Yang ,&nbsp;Qingyun Zhang ,&nbsp;Quanli Wu ,&nbsp;Xiaotong Ma ,&nbsp;Gusheng Tang ,&nbsp;Ming Guan ,&nbsp;Zhiyuan Wu","doi":"10.1016/j.cca.2025.120817","DOIUrl":"10.1016/j.cca.2025.120817","url":null,"abstract":"<div><h3>Background</h3><div>Calreticulin (CALR) exon 9 mutations are drivers in essential thrombocythemia (ET) and primary myelofibrosis (PMF). These mutations lead to extracellular secretion of mutant CALR, but a quantitative plasma assay to leverage this for management is lacking.</div></div><div><h3>Objective</h3><div>To develop and validate a quantitative method based on homemade monoclonal antibody (McAb) targeting mutant CALR for diagnosing ET and PMF, and evaluating therapeutic response in PEG-IFN-α-treated ET patients.</div></div><div><h3>Methods</h3><div>We generated a hybridoma clone (Cal26B11) producing anti-mutant CALR McAb and confirmed its reactivity via Western blot, immunofluorescence, and immunohistochemistry. Using Cal26B11 as the capture antibody, we developed a double-antibody sandwich ELISA (DAS-ELISA) to quantify plasma CALR mutant (pCALRmut). We assessed its diagnostic performance in 135 subjects (53 <em>CALR</em> type-1, and 37 type-2 mutant MPN patients, 11 non-<em>CALR</em>-mutated MPN patients, 9 non-MPN hematological malignancies, and 25 healthy donors) and conducted a 2-year follow-up of 49 CALR-mutant ET patients to evaluate its correlation with therapeutic response.</div></div><div><h3>Results</h3><div>Cal26B11 McAb showed high affinity (Kd = 5.90 × 10⁻¹⁰ M) and specificity for mutant CALR proteins. The established DAS-ELISA demonstrated good linearity (6.25–200 ng/ml) and sensitivity (LOQ: 7.78 ng/mL for type-1; 9.82 ng/ml for type-2 mutants). Using a cut-off of 15.98 ng/mL, the assay discriminated CALR-mutant from wild-type cases with 96.67 % sensitivity and 100 % specificity. Baseline pCALRmut concentrations rose step-wise from ET to pre-fibrotic MF and overt MF (<em>P</em> &lt; 0.0001). Although cross-sectional pCALRmut-VAF was weak, strong within-individual correlations during follow-up highlight its utility for serial monitoring. In patients treated with PEG-IFN-α, pCALRmut decreased in 76.5 % of cases, with a median reduction of 23.04 %, accompanied by a medium-to-long term complete hematological response (CHR) rate of approximately 75 %. Consistently, patients achieving CHR exhibited significantly lower pCALRmut levels than non-CHRs after PEG-IFN-α treatment, demonstrating a correlation between its dynamic reduction and treatment response.</div></div><div><h3>Conclusions</h3><div>The Cal26B11-based DAS-ELISA provides a reliable, non-invasive tool for detecting CALR mutations and shows promise for monitoring disease dynamics and treatment response, supporting its potential as a complementary biomarker. These preliminary findings warrant validation in larger prospective studies.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120817"},"PeriodicalIF":2.9,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905792","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}