Search Results (253)

The biomarker landscape in rheumatoid arthritis (RA) is evolving from reliance on traditional markers toward integrated, multimodal strategies enabling precision medicine approaches. To critically evaluate emerging biomarkers across serological, cellular, genetic, imaging, and multi-omic domains, distinguishing those approaching clinical readiness from those requiring further development. In this study, a narrative review of the literature published between 2000 and 2024 relevant to clinical decision-making in RA was conducted. Among novel serological markers, 14-3-3η protein and anti-carbamylated protein antibodies show the strongest validation for seronegative disease and prognostic stratification. Calprotectin demonstrates utility for disease activity monitoring and de-escalation decisions. Multi-biomarker disease activity scores provide an objective assessment but lack outcome trial validation. Musculoskeletal ultrasound offers accessible imaging biomarker capability, while MRI bone marrow edema remains the strongest structural progression predictor. Synovial tissue pathotyping has demonstrated proof-of-concept for treatment stratification. Genetic, epigenetic, and metabolomic approaches remain investigational. Key clinical implications include using 14-3-3η and calprotectin to inform seronegative diagnosis and de-escalation decisions, integrating ultrasound for remission verification, and recognizing that emerging biomarkers for extra-articular complications, including cardiovascular risk and venous thromboembolism, represent important unmet needs. Full article

Autoantibodies have long been regarded as passive reflections of immune dysregulation in connective tissue diseases (CTDs). Recent advances in systems immunology and molecular pathology have fundamentally redefined them as active molecular fingerprints that delineate distinct disease endophenotypes with predictive power for clinical trajectories and therapeutic responses. Rather than mere epiphenomena, autoantibodies encode precise information about dominant immune pathways, organ tropism, and pathogenic mechanisms. This review synthesizes emerging evidence that autoantibody repertoires—defined by specificity, structural properties, and functional characteristics—stratify patients beyond traditional clinical taxonomy into discrete pathobiological subsets. Specific signatures such as anti-MDA5 in rapidly progressive interstitial lung disease, anti-RNA polymerase III in scleroderma renal crisis, and anti-Ro52/TRIM21 in systemic overlap syndromes illustrate how serological profiles predict outcomes with remarkable precision. Mechanistically, autoantibody pathogenicity is modulated by immunoglobulin isotype distribution, Fc glycosylation patterns, and tissue-specific receptor expression—variables that determine whether an antibody functions as a biomarker or pathogenic effector. The structural heterogeneity of autoantibodies, shaped by cytokine microenvironments and B-cell subset imprinting, creates a dynamic continuum between pro-inflammatory and regulatory states. The integration of serological, transcriptomic, and imaging data establishes a precision medicine framework: autoantibodies function simultaneously as disease classifiers and therapeutic guides. This endophenotype-driven approach is already influencing trial design and patient stratification in systemic lupus erythematosus, systemic sclerosis, and inflammatory myopathies, and is reshaping both clinical practice and scientific taxonomy in CTDs. Recognizing autoantibodies as endophenotypic determinants aligns disease classification with pathogenic mechanism and supports the transition towards immunologically informed therapeutic strategies. Full article

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention. Full article

Introduction: A group of approximately 15 Candida species are frequently found to be responsible for human invasive candidiasis, an infection that appears in patients with prolonged hospitalization, particularly in Intensive Care Units, and in immunosuppressed individuals. Given the considerable burden if not rapidly treated, clinicians face diagnostic challenges in distinguishing infection. The objective of this narrative review is to summarize the clinically applicable biomarkers used for invasive candidiasis and to evaluate their performance and create a diagnostic algorithm for clinical practice. Methods: This narrative review was conducted by searching PubMed and Scopus for studies published between 1990 and 2025, using keywords related to invasive candidiasis and non-culture diagnostic biomarkers. Clinical guidelines and consensus documents from major infectious diseases societies were additionally reviewed to supplement. Results: Blood cultures, which are considered the “gold standard” for diagnosis, face important fallouts caused by the limited sensitivity of 50%. Polymerase Chain Reaction assays can identify Candida species at an early stage when compared to blood cultures, demonstrating high specificity that ranges between 91% and 98, due to their high cost, and the limitations regarding only the identification of certain species, their widespread use remains limited. Non-culture serological tests such as mannan, anti-mannan and 1-3-β-D-glucan can detect fungal cell wall components or antibodies directed towards them. These tests have the advantage of being performed directly from blood samples. Reported sensitivity and specificity are 83% and 86% for mannan/anti-mannan, and 73% and 80% for 1-3-β-D-glucan, respectively. They are used for early detection of candidemia in high-risk patients, including immunocompromised individuals. Conclusions: Our report suggests that the traditional “gold standard” for diagnosing invasive candidiasis can be improved by integrating and combining novel biomarkers in the diagnostic pathways, and, thus, potentially reducing the time spent for diagnosing and facilitating early treatment access. Full article

Background: Early prediction of gestational diabetes mellitus (GDM) remains a major clinical challenge, and the current oral glucose tolerance test (OGTT) is time-consuming and inconvenient for clinical routine. This study aimed to develop a novel predictive model for postprandial hyperglycemia GDM (pp-GDM) and postprandial glucose elevation using fasting serological and metabolic profiles. Method: We used High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) to analyze fasting plasma amino acid profiles at 24–28 weeks of gestation for 60 pp-GDM patients and 120 controls. Binary logistic regression model was constructed to identify potential biomarkers for pp-GDM prediction. Results: By incorporating amino acid indicators such as isoleucine, phenylalanine, threonine, and aspartate into the predictive model alongside traditional predictors (including BMI at sampling, fasting insulin, glycated hemoglobin, and uric acid), the overall predictive performance was significantly improved from 78.2% to 91.1%. A clinically practical nomogram for risk assessment was subsequently developed. Conclusions: This fasting metabolite-based model provides a reliable tool for early prediction of pp-GDM and postprandial hyperglycemia, which may reduce the need for OGTT and facilitate timely clinical decision making. Full article

Membranous nephropathy (MN) is an immune complex-mediated glomerular disease defined by sub-epithelial deposits that trigger complement activation and podocyte injury. Its pathogenesis reflects loss of immune tolerance and may present as a kidney-limited autoimmune process or in association with underlying conditions (e.g., malignancy, infection, drugs, or systemic autoimmunity). Current diagnostic work-up integrates circulating antibodies—most commonly anti–phospholipase A2 receptor 1 (PLA2R1)—and kidney biopsy, which remains essential in PLA2R1-negative or atypical presentations and for antigen confirmation when serology is negative. In PLA2R1-negative MN, an expanding list of antigens is being recognized, potentially refining phenotyping and risk assessment; however, dedicated studies remain limited, and the clinical weight of many newly described antigens likely requires further validation before supporting an antigen-based classification. Uneven access to advanced diagnostics particularly affects PLA2R1-negative cases, underscoring the need for centralized testing and the development of reliable non-invasive biomarkers. Treatment has advanced with rituximab and other targeted therapies, but resistant and relapsing cases remain challenging, and the evidence base for PLA2R1-negative forms is comparatively limited. This review summarizes recent diagnostic and therapeutic advances, focusing on PLA2R1-negative MN. Full article

Background/Objectives: Cancer Therapy-Related Cardiac Dysfunction (CTRCD) is a major complication in patients with non-Hodgkin lymphoma (NHL), potentially leading to heart failure and other severe cardiovascular events. Early identification of patients at risk is crucial for timely interventions. Methods: A prospective analytical cohort study was conducted on 127 adult NHL patients to evaluate chemotherapy-related cardiac dysfunction over a 6-month period, with the aim of assessing early adverse cardiac effects. Assessments included echocardiography, cardiorespiratory exercise testing, 24-h Holter monitoring, and measurement of cardiac-specific biomarkers (troponin I and NT-proBNP) to identify early subclinical cardiac changes. Results: A predictive model for CTRCD was developed using clinical, serological, echocardiographic, cardiopulmonary, and treatment-related parameters in patients with non-Hodgkin lymphoma. The model demonstrated high overall accuracy (94.2%) and strong discriminative ability (AUC 0.95; precision-sensitivity AUC 0.824) for 6-month cardiotoxicity. SHAP analysis identified the most influential predictors as baseline SDNNi, mean daily heart rate, total doxorubicin dose, NT-proBNP, QT corrected interval, hemoglobin, age, left atrial volume, and diastolic function indices (E/e′, E/A). Lower cardiopulmonary reserve was also associated with increased risk. Conclusions: The predictive model developed in this study serves as a practical and robust tool for assessing the risk of cancer therapy-related cardiac dysfunction. Full article

Primary biliary cholangitis (PBC) is a heterogeneous autoimmune liver disease in which clinical presentation, disease progression, and response to therapy vary markedly from patient to patient. This heterogeneity reflects its complex, multifactorial, and not-completely elucidated pathogenesis. Currently, serological markers are available to non-invasively diagnose PBC, reserving liver biopsy for selected cases with atypical presentations or diagnostic uncertainty. Anyway, the accurate non-invasive prediction of liver-related and non-liver-related (i.e., extra-hepatic, including pruritus) outcomes remains an open challenge, as well as an urgent need, considering the great variability in clinical course and prognosis reported in PBC patients. Moreover, although ursodeoxycholic acid (UDCA) remains the standard first-line treatment, not all individuals respond equally, either in terms of therapeutic efficacy or timing of biochemical improvement. This further variability in treatment response underscores the inadequacy of uniform management approaches and reinforces the urgent need for personalized medicine, where treatment decisions are guided by patient-specific biological and clinical parameters. In this scenario, the identification and validation of non-invasive predictive biomarkers capable of detecting early therapeutic responsiveness are pivotal for optimizing care pathways. Finally, a growing portion of patients show an insufficient UDCA response or are UDCA intolerant, making the identification of novel strategies of care an urgent need. Concerning this, very recently, new therapeutic options beyond UDCA targeting, among the other pathways, bile acid metabolism (including the modern Peroxisome Proliferator-Activated Receptor agonists), immune regulation, and fibrogenesis, have expanded the treatment landscape. In the Era of Precision Medicine, these diagnostic, prognostic, and therapeutic innovations, by reflecting the complexity of PBC pathogenesis, underline the cruciality of a patient-tailored strategy to improve outcomes and mitigate disease progression. The present review reports recent advances, highlights ongoing challenges, and outlines future perspectives in the management of PBC. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. PBC encompasses several clinical subtypes, including classical AMA-positive PBC (90–95% of cases), AMA-negative PBC (5–10%), and overlap syndromes such as AIH-PBC. These subtypes exhibit distinct serological profiles, with AMA-negative cases often presenting PBC-specific antinuclear antibodies (anti-gp210, anti-sp100) and overlap syndromes demonstrating combined autoantibody patterns characteristic of both conditions. Autoantibodies serve as central biomarkers for diagnosis, prognosis, and understanding disease pathogenesis. This review provides a comprehensive overview of classical and emerging autoantibodies associated with PBC, including AMA-M2, anti-gp210, anti-sp100, anti-KLHL12, and anti-RPL30. We discuss their diagnostic significance across PBC subtypes, pathogenic implications, and potential utility in patient stratification and therapeutic monitoring. Recent evidence suggests that bile acid-induced neoantigen formation, rather than classical loss of immune tolerance, may drive AMA production. Advances in autoantibody profiling, including subclass-specific analysis and multi-marker panels, may pave the way for personalized medicine and improved outcomes in PBC. Full article

Non-coeliac wheat sensitivity (NCWS) is characterised by gastrointestinal and extra-intestinal symptoms following gluten/wheat ingestion in individuals without coeliac disease or wheat allergy but remains controversial due to symptom overlap with irritable bowel syndrome (IBS). This narrative review aims to provide a comprehensive, critical analysis of NCWS as a clinical and biological entity, examining the evidence for its distinction from related disorders. While self-reported rates are high (often >10%) in the general population, rigorous double-blind, placebo-controlled challenge (DBPCC) studies confirm the diagnosis in only a minority of cases (typically <30%). The clinical presentation is heterogeneous, combining IBS-like symptoms with systemic complaints such as “brain fog,” headaches, and fatigue. The pathophysiology is distinct from coeliac disease, involving innate immune activation, altered intestinal barrier function, and gut dysbiosis. Non-gluten wheat components, particularly fructans and amylase-trypsin inhibitors, are implicated as potential triggers. Diagnosis is challenging, requiring the exclusion of other disorders and adherence to complex dietary challenge protocols such as the Salerno Experts’ Criteria, which are impractical for routine clinical use. The search for validated biomarkers is a key research area and investigated candidates include serological markers such as IgG anti-gliadin antibodies, inflammatory markers such as faecal calprotectin, and proteins related to intestinal permeability such as zonulin, but results have been conflicting and require further validation. Management primarily involves elimination of wheat and gluten from the diet, although a low-FODMAP diet has also proven effective as an adjunctive treatment. In conclusion, NCWS is a clinical entity whose study and management are critically hampered by the absence of validated diagnostic criteria and biomarkers. Progress requires methodologically rigorous DBPCC trials to elucidate its mechanisms and develop reliable diagnostic tools. Full article

Antibodies against the human papillomavirus type 16 (HPV16) E6 oncoprotein are promising biomarkers for the early detection of HPV-driven oropharyngeal squamous cell carcinoma (HPV+OPSCC). Standard serologic testing is challenging in underserved regions with high HPV+OPSCC incidence. Dried blood spot (DBS) cards offer a low-resource alternative but remain unevaluated for HPV antibody detection. A total of 25 OPSCC patients who provided paired serum (venipuncture) and DBS (finger-prick) samples were recruited from the University of Kentucky. HPV16 antibodies (L1, E1, E2, E4, E6, E7) were measured using multiplex serology, quantified as median fluorescence intensity (MFI) and dichotomized using established cutoffs. Correlation between serum and DBS MFI values was evaluated using linear regression and Bland–Altman plots, whereas sensitivity, specificity, and Cohen’s kappa assessed agreement. Mean MFI levels were lower in DBS than serum but were strongly correlated (R = 0.73 to 0.96; HPV16 E6 = 0.83). For HPV16 E6, DBS sensitivity was 90% (95% CI: 68–99) and specificity 100% (95% CI: 48–100), with kappa = 0.787. Specificity was 100% across all markers, while sensitivity varied from 0% (L1) to 100% (E2). DBS cards are accurate, inexpensive, and a scalable alternative for HPV16 E6 antibody detection, particularly in medically underserved regions, though further validation is needed. Full article

Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability. Full article

Artificial intelligence (AI) is rapidly transforming rheumatology, particularly in imaging and laboratory diagnostics where data complexity challenges traditional interpretation. This narrative review summarizes current evidence on AI-driven tools across musculoskeletal ultrasound, radiography, MRI, CT, capillaroscopy, and laboratory analytics. A structured literature search (PubMed, Scopus, Web of Science; 2020–2025) identified 90 relevant publications addressing AI applications in diagnostic imaging and biomarker analysis in rheumatic diseases, while twelve supplementary articles were incorporated to provide contextual depth and support conceptual framing. Deep learning models, notably convolutional neural networks and vision transformers, have demonstrated expert-level accuracy in detecting synovitis, bone marrow edema, erosions, and interstitial lung disease, as well as in quantifying microvascular and structural damage. In laboratory diagnostics, AI enhances the integration of traditional biomarkers with high-throughput omics, automates serologic interpretation, and supports molecular and proteomic biomarker discovery. Multi-omics and explainable AI platforms increasingly enable precision diagnostics and personalized risk stratification. Despite promising performance, widespread implementation is constrained by significant domain-specific validation gaps, data heterogeneity, lack of external validation, ethical concerns, and limited workflow integration. Clinically meaningful progress will depend on transparent, validated, and interoperable AI systems supported by robust data governance and clinician education. The transition from concept to clinic is under way—AI will likely serve as an augmenting rather than replacing partner, standardizing interpretation, accelerating decision-making, and ultimately facilitating precision, data-driven rheumatologic care. Full article

Acute Myocardial Infarction (AMI) is a critical cardiac condition that poses a substantial threat to myocardial function. Expedient diagnosis of AMI is paramount and relies on serological assays for rapid and accurate quantification of relevant biomarkers. Electrochemical sensors have emerged as promising candidates for this application, owing to their accessibility, operational simplicity, and high specificity. In this study, we developed a paper-based electrochemical immunosensor to detect cardiac troponin I in serum and saliva specimens. The electrode was fabricated using screen-printing technology with photographic paper as the substrate, employing graphite-based ink, nail polish, and acetone as the solvent. A quasi-reference electrode was constructed using silver powder-based ink, nail polish, and acetone. The immunosensor was prepared by modifying the working electrode with gold nanoparticles (AuNP) functionalized with cardiac troponin I antibodies (anti-cTnI) and bovine serum albumin (BSA). This modified electrode was subsequently used to detect the troponin I antigen. The analyses were performed in 0.1 mol L⁻¹ phosphate buffer medium, pH 7.00, in the presence of 5.0 mmol L⁻¹ of the potassium ferrocyanide probe. The immunosensor exhibited a sensitivity of 0.006 µA/fg mL⁻¹, a limit of detection of 9.83 fg mL⁻¹, and a limit of quantification of 32.79 fg mL⁻¹. Specificity studies conducted in the presence of other macromolecules demonstrated minimal interference, with relative standard deviations (RSD) below 5.00%, indicating a specific interaction with troponin I. Furthermore, the immunosensor demonstrated excellent reproducibility and stability. Upon application to serum and saliva samples, the immunosensor presented recoveries of approximately 99–105%, suggesting its potential applicability in clinical analyses. Full article

Rabies is endemic in Kazakhstan, with the primary reservoirs being wild canids, such as foxes and dogs, maintaining distinct sylvatic and urban cycles. This paper outlines three high-return priorities for rabies control in the country, informed by the epidemiological patterns of the disease, the national regulatory framework (Order No. 7-1/587), and evidence on the knowledge, attitudes, and practices (KAP) of the Kazakh population. The three priorities are (a) transition into a One Health, real-time surveillance system featuring standardized digital reporting and GIS-guided interventions; (b) implementation of biannual oral rabies vaccination (ORV) of foxes in high-risk districts, incorporating mandatory quality assurance (via tetracycline biomarkers and/or serology) aligned with EU/EFSA standards; and (c) adopt an urban strategy focused on dogs to increase vaccination coverage and reduce delays in human post-exposure prophylaxis (PEP). These measures align with the WOAH Terrestrial Code and the “Zero by 30” roadmap, leveraging existing national assets like risk maps and laboratory capacity, such as dFAT, RT-PCR, and sequencing. Kazakhstan’s predictable rabies pattern allows for targeting district-level strategies and transparent measurement of risk reduction, contingent on enforcing standardized reporting and rigorous quality assurance programs. The opinions introduced in this paper are based on the scientific evidence collected in Kazakhstan over the last decade and summarize the need for urgent actions to promote rabies control in the country. Full article