Clinica Chimica Acta最新文献

{"title":"Non-coding RNA biomarkers in Alzheimer’s disease","authors":"Mozhdeh Mohammadpour ,&nbsp;Kholoud Saeidi ,&nbsp;Felora Ferdosi ,&nbsp;Hadi Khanifar ,&nbsp;Ehsan Dadgostar ,&nbsp;Faranak Zakizadeh ,&nbsp;Siavash Abdolghaderi ,&nbsp;Seyyed Hossein Khatami","doi":"10.1016/j.cca.2025.120427","DOIUrl":"10.1016/j.cca.2025.120427","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most prevalent cause of dementia among elderly individuals and is characterized by progressive cognitive decline, memory impairment, and the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles in the brain. Despite extensive research, current therapeutic approaches remain limited to symptomatic relief and are unable to halt disease progression. This challenge highlights the urgent need for reliable biomarkers that enable early diagnosis and facilitate the development of targeted interventions. Noncoding RNAs (ncRNAs) have recently emerged as promising biomarkers because of their regulatory roles in gene expression and cellular function. Among them, microRNAs (miRNAs) have revolutionized our understanding of neurodegenerative processes, with evidence linking their dysregulation to AD pathology. Additionally, circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) have been implicated in neuronal survival, synaptic maintenance, and amyloid precursor protein processing, further expanding the biomarker landscape. This review examines the expression patterns, functional significance, and diagnostic potential of ncRNAs in AD, alongside methodological approaches for their detection. By bridging molecular insights with translational applications, we explore how ncRNAs may redefine AD diagnostics and therapeutic strategies in the future.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120427"},"PeriodicalIF":3.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281033","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":"Circular RNA biomarkers in cardiovascular disease","authors":"Tursunova Nozima ,&nbsp;Nassyrova Nargiza Batyrkhankyzy ,&nbsp;Mustafa Jawad Kadham ,&nbsp;Khamidova Aziza Abdufattoevna ,&nbsp;Alijon Khatamov ,&nbsp;Pulatova Shaxnoza Khaydarova ,&nbsp;Ibragimkhodjaev Bakhodir ,&nbsp;Rasulova Nodira Alisherovna ,&nbsp;Kholmurodova Dilafruz Kuvatovna ,&nbsp;Khidoyatova Mukhlisa ,&nbsp;Kudeshova Gulchekhra ,&nbsp;Bobojonov Otabek ,&nbsp;Matkarimov Inomjon","doi":"10.1016/j.cca.2025.120424","DOIUrl":"10.1016/j.cca.2025.120424","url":null,"abstract":"<div><div>Despite medical advancements, heart disease continues to be a primary cause of death globally. While early detection and continuous monitoring are essential for better patient outcomes, current biological markers, such as cardiac troponins and BNP, have shortcomings, including their temporary nature and susceptibility to various factors, such as patient age and other medical conditions. This limitation has motivated scientists to identify new biological indicators and treatment targets that better represent the underlying heart disease mechanisms. Circular RNAs (circRNAs) have recently been identified as key regulatory molecules in various illnesses, including cardiac conditions. These unique noncoding RNA molecules feature a closed circular structure that makes them exceptionally stable and resistant to breakdown. Their durability, specific expression patterns in different tissues, and preservation across species make them promising candidates both as disease markers and potential therapeutic tools for heart conditions. The scientific interest in the role of circRNAs in cardiovascular disease has increased significantly, with studies revealing their involvement in controlling genes and disease development. This comprehensive review examines circRNAs in heart disease, covering their formation, functional mechanisms, and potential clinical applications as disease markers. This paper discusses recent scientific discoveries highlighting their value in diagnosis and prognosis, addresses the difficulties in moving these findings into medical practice and explores future possibilities for the use of circRNAs in heart disease diagnosis and treatment.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120424"},"PeriodicalIF":3.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281032","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":"Diagnostic and prognostic biomarkers in Polycystic Ovary Syndrome","authors":"Ishanka Singh,&nbsp;Kareena Moar,&nbsp;Pawan Kumar Maurya","doi":"10.1016/j.cca.2025.120425","DOIUrl":"10.1016/j.cca.2025.120425","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is most common reproductive- endocrine disorder with extensive clinical phenotypes. It is characterized by hyperandrogenism, anovulation, and polycystic ovarian morphology. Despite its high prevalence globally, the etiology of PCOS remains unresolved. The clinical diagnosis remains largely based on heterogeneous clinical criteria rather than objective molecular indicators. This variability often leads to delayed or inaccurate diagnosis. There is a critical need to identify reliable biomarkers that can support early and precise detection. This review summarizes current findings on a broad spectrum of biomarkers associated with PCOS, drawing from peer-reviewed literature spanning the last two decades. We categorized the biomarkers into five major domains: hormonal, metabolic, oxidative stress, inflammatory, and microRNA-related biomarkers. Hormonal disturbances include high luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratios and elevated Anti Müllerian hormone (AMH) are important biomarkers for reproductive disturbance in PCOS. Metabolic markers, including insulin, triglycerides, apolipoprotein B, and decreased sex hormone-binding globulin (SHBG) levels, represent patterns of insulin resistance and dyslipidemia. The shift in an adipokine profile with elevated leptin and lower adiponectin levels highlights metabolic dysfunction. Biomarkers of oxidative stress, such as malondialdehyde (MDA), nitric oxide, indicate a pro-oxidant-antioxidant imbalance. Chronic systemic inflammation is also observed as inflammatory markers (CRP and TNF-α) were present. These biomarkers collectively reveal molecular aspects of PCOS and suggest innovative opportunities for diagnostic accuracy enhancement and personalized therapeutic approaches. Our review highlights the need for the incorporation of multi-dimensional biomarker profiles in clinical practice to improve the capture of the heterogeneity of PCOS.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120425"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291426","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":"Molecular and clinical characteristics of pediatric patients with primary congenital hypothyroidism: novel genetic variants and the genotype-phenotype association.","authors":"Cheng-Cheng Zhang, Wen-Ting Zhang, Li-Hua Chen, Mei Deng, Jing-Li Tian, Rui Liu, Jing-Jing Ma, Xiao-Ling Huang, Yuan-Zong Song","doi":"10.1016/j.cca.2025.120426","DOIUrl":"https://doi.org/10.1016/j.cca.2025.120426","url":null,"abstract":"<p><strong>Background and aims: </strong>Primary congenital hypothyroidism (CH) was classified into thyroid dysgenesis(TD) and thyroid dyshormonogenesis(TDH) based on pathophysiology, and into permanent CH (PCH) and transient CH (TCH) based on outcomes after age two. Despite progress in identifying pathogenic genes and genetic variants, the genetic characteristics and genotype-phenotype correlations remained insufficiently explored. This study aimed to identify novel variants, assess their pathogenicity, and analyze the correlation between genotype and phenotype.</p><p><strong>Subjects and methods: </strong>Clinical data from 97 pediatric patients with primary CH were collected (32 previously reported, 65 newly diagnosed). Next-generation sequencing was used to screen for variants, and statistical analysis was performed on the clinical data.</p><p><strong>Results: </strong>Genetic etiologies were identified in 48% of patients, with 91% associated with TDH and 9% with TD. Six genes were involved: DUOX2 (68%), DUOXA2 (9%), TPO (9%), TG (6%), PAX8 (6%), and TSHR (2%). Seven novel variants were identified, including two pathogenic and five likely pathogenic. The TD-positive rate was significantly higher in the PCH group (43%) compared to the TCH group (0%). Genotype-phenotype analysis revealed that, at diagnosis, free thyroxine (FT4) levels were significantly lower in the genetic CH group compared to the carrier and wild-type groups. Additionally, the DUOX2 group had significantly higher free triiodothyronine (FT3) and FT4 levels at diagnosis compared to the non-DUOX2 group.</p><p><strong>Conclusions: </strong>This study highlighted the significant role of genetic factors in primary CH, with DUOX2 being the most common pathogenic gene. Seven novel variants were identified, expanding the genetic spectrum. TDH might have been the main pathogenic mechanism, and TD was closely linked to PCH. Genetic CH was associated with lower FT4 levels, while DUOX2 variants correlated with milder biochemical phenotypes, further supporting genotype-phenotype correlations.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120426"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293443","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":"Practical sustainable laboratory medicine.","authors":"Tony Badrick, Guzin Aykal, Tuija Mannisto, John Anetor","doi":"10.1016/j.cca.2025.120428","DOIUrl":"https://doi.org/10.1016/j.cca.2025.120428","url":null,"abstract":"<p><p>Medical laboratories now face the challenge of sustainability. Many publications provide evidence of healthcare's impact on the environment and, increasingly, specific laboratory-focused examples. However, few documents guide how to plan to reduce the impact on the environment. This paper aims to provide some practical steps that a laboratory can use to reduce waste and environmental impact. The six steps are Step 1: Awareness - Look Around; Step 2: Form a green team of like-minded green champions - Think Green; Step 3: Develop a laboratory-wide action plan to reduce waste - Small Steps, Big Impacts; Step 4: Incorporate environmental management into the laboratory's operational and strategic planning - Integrate Sustainable Practices; Step 5: Seek EFLM Green and Sustainable Laboratory Certification or MyGreenLab Certification - Be Proud and Show It; and, Step 6: From Certification to Culture/ Sustaining Sustainability - Make a Difference. These laboratory initiatives have broader health care system benefits for countries. The paper also describes Green Chemistry, which refers to the design of chemical products and processes that reduce or eliminate the generation of hazardous substances. The concept applies across the life cycle of chemical products, including their design, manufacture, use and ultimate disposal. Adopting this approach provides a laboratory's Environmental, Social, and Governance framework.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120428"},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293444","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":"Determination of testosterone by liquid Chromatography–Tandem mass spectrometry in dried plasma obtained from capillary blood using the HealthID PSD microsampling device","authors":"Amanda Pacheco Bondan ,&nbsp;Ana Paula Grando ,&nbsp;Eduarda Milena Reichert ,&nbsp;Giovana Piva Peteffi ,&nbsp;Giovanna da Silva Grassi ,&nbsp;Maitê de Moraes Machado ,&nbsp;Roberta Zilles Hahn ,&nbsp;Marina Venzon Antunes ,&nbsp;Eduardo Guimarães Camargo ,&nbsp;Mariele Feiffer Charão ,&nbsp;Rafael Linden","doi":"10.1016/j.cca.2025.120421","DOIUrl":"10.1016/j.cca.2025.120421","url":null,"abstract":"<div><div>Monitoring testosterone (T) levels is essential in various clinical contexts, but traditional venous sampling is invasive and limits access. This study describes the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify T in dried plasma spot (DPS) samples obtained from capillary blood using the HealthID PSD microsampling device. A chloride-based correction of plasma volume in the DPS and a multiplication factor were applied to estimate venous plasma concentrations. The method showed linearity from 1.63 to 104.02 nmol/L, with accuracy ranging from 96.8 % to 105.2 % and precision between 1.90 % and 7.24 %. Matrix effects were adequately corrected by the internal standard, and extraction yield exceeded 89 %. T in DPS samples was stable for up to 10 days at room temperature and 40 °C. Clinical validation involved 104 volunteers, including cisgender men and transgender individuals on hormone therapy. A strong correlation was observed between DPS-derived and venous plasma testosterone levels (<em>r</em> = 0.950), and the percent total error (TE%) of 16.41 % met the desirable performance criterion derived from biological variation data. The method proved robust against hematocrit variation and sample volume differences. This is the first report on T quantification using a capillary plasma separation device, highlighting the potential of the HealthID PSD for simplified, decentralized T monitoring. The approach offers practical advantages in collection, transport, and storage, making it a promising alternative to conventional phlebotomy for clinical applications.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120421"},"PeriodicalIF":3.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263492","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":"Genetic landscape of primary ovarian insufficiency in Bangladeshi women through whole exome sequencing","authors":"Hasna Hena Pervin ,&nbsp;Rabeya Akter Mim ,&nbsp;Athoi Ganguly ,&nbsp;Rezaul Karim Kazal ,&nbsp;Rohit Gutgutia ,&nbsp;Tamannyat Binte Eshaque ,&nbsp;Farjana Binta Omar ,&nbsp;Md.Atikur Rahaman ,&nbsp;Md.Nahid Hasan ,&nbsp;Amirul Islam ,&nbsp;Nasna Nassir ,&nbsp;Mohammad Shahnoor Hossain ,&nbsp;Hosneara Akter ,&nbsp;Mohammed Uddin","doi":"10.1016/j.cca.2025.120423","DOIUrl":"10.1016/j.cca.2025.120423","url":null,"abstract":"<div><h3>Background</h3><div>Primary Ovarian Insufficiency (POI), a significant cause of female infertility, involves premature ovarian dysfunction before the age of 40 and is influenced by genetic predispositions, autoimmune disorders, environmental factors, and metabolic changes. In this study, we employed Whole Exome Sequencing (WES) to explore genetic variations linked to POI in Bangladeshi women.</div></div><div><h3>Materials and methods</h3><div>This study encompassed 30 Bangladeshi women aged 16 to 40 diagnosed with POI. The diagnosis was based on clinical criteria, including elevated Follicle-Stimulating Hormone levels and a history of at least four months of oligomenorrhea or amenorrhea. WES was performed on POI cases and used population specific internal cohort to filter out and identify genes impacting ovarian function. Subsequently, Sanger Sequencing was used to validate pathogenic or likely pathogenic variants.</div></div><div><h3>Results</h3><div>We detected seven pathogenic variants in 23% of all POI cases (7/30) across six genes: Thyroglobulin (<em>TG</em>)<em>,</em> Thyroid-Stimulating Hormone Receptor (<em>TSHR</em>)<em>,</em> tubulin beta 8 class viii (<em>TUBB8</em>)<em>,</em> PR/SET domain 9 (<em>PRDM9</em>)<em>,</em> required for meiotic nuclear division 1 homolog (<em>RMND1</em>)<em>,</em> and homologous recombination factor with OB-fold (<em>HROB</em>). Two novel likely pathogenic variants were identified, including a heterozygous frameshift variant in <em>TG</em> (p.H209Pfs11) and a heterozygous missense variant in <em>TSHR</em> (p.T1904C). Additionally, variants of uncertain significance were found in 63% (19/30) of the cases, with seven being novel. Incidental findings of pathogenic variants were observed in several genes, with Hemoglobin subunit Beta (<em>HBB</em>) being the most common.</div></div><div><h3>Conclusions</h3><div>This study highlights the utility of whole exome sequencing in identifying genetic risk factors for POI, suggesting that incorporating genetic screening into routine clinical practice could improve diagnostic and therapeutic strategies, particularly in regions lacking genomic data on this condition.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120423"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263493","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":"An integrated framework for universal coagulation test reference intervals: Cross-platform validation of eleven indirect algorithms and age-specific hierarchical optimization","authors":"Yunfeng Wu ,&nbsp;Tingting Huang ,&nbsp;Huixian Huang,&nbsp;Fan Yu,&nbsp;Jiao Liu,&nbsp;Xi Tang,&nbsp;Lei Chen,&nbsp;Yiwen Zhou,&nbsp;Haihong He","doi":"10.1016/j.cca.2025.120422","DOIUrl":"10.1016/j.cca.2025.120422","url":null,"abstract":"<div><h3>Background</h3><div>The conventional direct method for establishing coagulation reference intervals (RIs) faces challenges, including difficulties in recruiting healthy populations, non-Gaussian distributions, and complex age-related effects. Indirect methods utilizing real-world data (RWD) are limited by a lack of consensus on algorithm selection and insufficient cross-platform validation.</div></div><div><h3>Objective</h3><div>To develop a multi-algorithm collaborative framework for systematically evaluating the performance of 11 outlier detection algorithms, thereby optimizing coagulation RIs for the Chinese population and validating their cross-platform applicability.</div></div><div><h3>Methods</h3><div>We retrospectively analysed 630,946 coagulation test records from Shenzhen Hospital of Southern Medical University. Outlier removal was performed using eleven algorithms. Algorithm stability and sex/age effects were quantified via reference change value (RCV) and variance component models. Validation was conducted across Mindray CX-9000 and Stago STA R Max platforms.</div></div><div><h3>Results</h3><div>Among the 11 algorithms, Z-Score and Tukey demonstrated optimal performance for 8 coagulation parameters, yielding RIs with minimal deviation from manufacturer standards. Sex-based analysis revealed minimal differences (Standard deviation ratio (SDR) &lt; 0.40, Standardized effect size (Cohen’s d) &lt;0.50), eliminating the need for sex stratification. Age stratification was required for D-Dimer (≥60 years subgroup: SDR = 0.62, Cohen’s d = 0.54). Cross-platform consistency confirmed algorithm generalizability.</div></div><div><h3>Conclusions</h3><div>This RCV-driven multi-algorithm framework establishes the Z-Score and Tukey methods as optimal for coagulation RIs derivation, advocates age-specific D-Dimer RIs, and deems sex stratification unnecessary. This scalable approach enhances standardization in coagulation testing.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120422"},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254102","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":"Comparison of four indirect methods for establishing sex- and age-specific reference intervals for IgG: based on real world data","authors":"Wensong Liu ,&nbsp;Zhixian Xie ,&nbsp;Meng Wang ,&nbsp;Zhixuan Guo ,&nbsp;Qian Zhang ,&nbsp;Lijuan Wang ,&nbsp;Jiaqi Zhang ,&nbsp;Xiaoshuang Zhu ,&nbsp;Chuanbao Li ,&nbsp;Shunli Zhang","doi":"10.1016/j.cca.2025.120420","DOIUrl":"10.1016/j.cca.2025.120420","url":null,"abstract":"<div><h3>Objective</h3><div>To compare four indirect methods for establishing sex- and age-specific reference intervals (RI) for adult serum immunoglobulin G (IgG) based on real world data.</div></div><div><h3>Methods</h3><div>All serum IgG measurement results from 2020 to 2021 in Beijing Hospital were collated. Following data screening, four indirect methods were applied to calculate the RI of the total population, different sexes, ages and seasons (months). The results were then compared with the manufacturer’s RI and National Industry Standard in China to verify the reliability of the RI obtained in this study. The minimal allowable bias of the CV of the RI and the permissible difference (pD) elaborated by the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) were used as the criterion.</div></div><div><h3>Results</h3><div>A total of 13,162 data points were obtained. There were significant differences between men and women within the RI calculated by four methods. With increasing age, the upper limit of RI (URL) increased and the lower limit reference (LRL )decreased. However, there was no obvious trend in different seasons. The LRL of the four methods were within the pD based on manufacturer’s RI, while the URL of the Hoffmann and RefineR methods conformed to the pD based on the National Industry Standard’s RI, and neither the RI of the National Industry Standard nor the manufacturer's were within the minimal allowable bias of the CV of the RI with our study.</div></div><div><h3>Conclusions</h3><div>The serum IgG RI were established by four indirect method. The significant differences were found between males and females, younger and older. Clinical laboratories should establish their own RI in order to better diagnose and treat disease.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120420"},"PeriodicalIF":3.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265397","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":"Beta-2 microglobulin in lymphoma","authors":"Gaurav Gupta ,&nbsp;Muhammad Afzal ,&nbsp;Ahsas Goyal ,&nbsp;G. PadmaPriya ,&nbsp;Manish Srivastava ,&nbsp;Kattela Chennakesavulu ,&nbsp;Biswaranjan Mohanty ,&nbsp;A. Rekha ,&nbsp;Avijit Mazumder ,&nbsp;Kavita Goyal ,&nbsp;Haider Ali ,&nbsp;Moyad Shahwan","doi":"10.1016/j.cca.2025.120418","DOIUrl":"10.1016/j.cca.2025.120418","url":null,"abstract":"<div><div>Lymphomas are heterogeneous hematologic malignancies characterised by the abnormal proliferation of lymphocytes. β₂-Microglobulin (β₂M) functions both as a structural subunit of primary histocompatibility complex class I (MHC I) and as a circulating biomarker with established diagnostic and prognostic significance. Serum β₂M &gt; 2.5 mg/L is elevated in 60 % of mantle cell lymphoma and in &gt; 50 % of advanced-stage diffuse large B-cell lymphoma, correlating with higher tumor burden, International Prognostic Index scores, and inferior survival; cerebrospinal fluid β₂M enhances central nervous system lymphoma diagnosis with 97 % sensitivity and specificity. Mechanistically, β₂M stabilizes MHC I to enable CD8⁺ T-cell antigen presentation and, when shed, activates JAK/STAT and NF-κB pathways that drive tumor proliferation and immune evasion. Preclinical strategies targeting these β₂M-driven signals such as anti-β₂M antibodies combined with proteasome inhibitors demonstrate enhanced cytotoxicity in resistant models. Advanced three-dimensional scaffold culture platforms preserve β₂M-tumour-immune interactions, allowing for the investigation of matrix stiffness effects on signalling. Emerging mechanotherapy approaches leverage extracellular matrix rigidity to modulate β₂M-related pathways and sensitize lymphoma cells to therapy. The remaining challenges include assay standardization, cohort variability, and lack of prospective validation of β₂M-based indices. Future efforts should focus on harmonising β₂M measurement methods and integrating mechanistic insights into refined risk stratification and therapeutic strategies.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"576 ","pages":"Article 120418"},"PeriodicalIF":3.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241404","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}