Search Results (594)

Background: Chronic urticaria (CU) is a complex skin condition, frequently challenging both patients and clinicians and requiring wise individualized management. While allergy, autoimmunity, and depression are recognized comorbidities, evidence linking CU and malignancy remains underexplored. Screening for malignancy is not a routine standard of care for CU patients. Methods: A literature review was conducted to explore the potential risk or associations, including immune mechanisms, between CU and malignancy, based on searches in the PubMed and Google Scholar databases. Results: Scientific evidence on the malignancy risk in CU and its causal relationship is limited to a few population-based studies and case reports. A higher incidence of hematologic malignancy in CU patients has been reported in several publications, but the overall risk of malignancy in the CU population remains controversial. Antihistamine resistance, ultra-low IgE, and older age at the time of CU diagnosis may be related to a higher risk of malignancy, especially shortly after CU diagnosis. Immunological pathways linking CU and cancer are not clear. Immune system dysregulation, including alterations in immune checkpoints, is a feature of both cancer and CU. Such dysregulation may promote immunotolerance, abnormal immune responses, and mast cell activation through novel autoantigens and autoantibodies involved in the tumor microenvironment. Conclusions: There is growing, although limited, evidence suggesting a possible link between CU and malignancy, especially hematologic cancers. Large multicenter cohort studies are warranted to determine whether CU may act as a clinical harbinger of malignancy and to identify patient subsets that may benefit from targeted cancer screening. Full article

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory infection characterized by significant inflammatory responses and lung tissue injury. However, the precise immunological mechanisms and temporal dynamics of key cytokines driving pulmonary inflammation in MPP are still unclear. This study aimed to investigate the underlying immunological mechanisms and cytokine dynamics in MPP. We established an acute MPP murine model via intranasal administration of M. pneumoniae. This model recapitulates key features of human MPP, such as robust airway inflammation and cytokine production. Comprehensive analyses were conducted, including histopathology, flow cytometry, and cytokine profiling. Results showed severe inflammatory responses with prominent infiltration of neutrophils and macrophages in lung tissue, whereas monocyte populations were significantly reduced, indicating a shift towards myeloid cell predominance. Notably, 36 cytokines, including pro-inflammatory interleukins (IL-1β, IL-6, IL-17A) and chemokines, were statistically significantly upregulated in bronchoalveolar lavage fluid compared to the normal group, highlighting a cytokine storm associated with lung inflammation and tissue damage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis further revealed enriched pathways related to cytokine-cytokine receptor interactions and IL-17 signaling, suggesting potential therapeutic targets. In conclusion, this study preclinical provides insights into the innate immune response and cytokine-driven pathology in acute MPP, underscoring the pivotal roles of myeloid cells and pro-inflammatory cytokines. Future research should focus on clinical validation of these findings to assess their translational potential and the exploration of immunomodulatory strategies informed by this model to mitigate MPP severity. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Background/Objectives: Acute generalized exanthematous pustulosis (AGEP) is a severe drug-induced cutaneous reaction characterized by the abrupt onset of sterile pustules, fever, neutrophilia, and a T cell-mediated type IVd hypersensitivity response. This narrative review synthesizes current evidence on pharmacological triggers, immunopathogenic mechanisms, diagnostic criteria, and differential diagnosis to provide a clinically oriented framework. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ScienceDirect, and SpringerLink for studies published between 2000 and 2025, complemented by selected clinical reference sources. Studies addressing clinical features, immunological pathways, pharmacovigilance signals, and diagnostic tools for AGEP were included. Synthesis of Evidence: β-lactam antibiotics remain the most frequent triggers, while increasing associations have been reported with hydroxychloroquine, targeted therapies, immune checkpoint inhibitors, psychotropic agents, and vaccines. Immunopathogenesis is driven by IL-36 activation, CXCL8/IL-8–mediated neutrophil recruitment, and IL36RN mutations, explaining overlap with pustular psoriasis. Diagnostic accuracy improves through integration of drug latency, clinical morphology, histopathology, biomarkers, and standardized tools such as the EuroSCAR score. Conclusions: AGEP is a complex pustular reaction induced by diverse drugs and amplified by IL-36-mediated inflammation. Accurate diagnosis requires a multidimensional approach supported by structured algorithms and robust pharmacovigilance to identify evolving drug-associated patterns. Full article

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

Background/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air–liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade. Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45⁺ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti–PD-1) to assess local immune modulation. Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC–Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour–immune interactions. Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour–immune interactions. Full article

Background: Oncological treatment remains a major clinical challenge. Despite therapeutic advances and the diversity of available approaches, many tumors continue to exhibit limited responsiveness to chemotherapy. In this context, nutrition has emerged as a promising complementary strategy to support cancer therapy. In particular, interventions based on nutritional deprivation have gained prominence due to their ability to modulate tumor metabolism, inducing alterations that may increase the sensitivity of cancer cells to conventional treatments. Accordingly, the present study aimed to evaluate the safety and efficacy of caloric restriction combined with chemotherapy in a Sarcoma-180 model, investigating its effects on immunological and hematological parameters, antioxidant activity, oxidative stress, and tumor and liver morphology, as well as DNA damage. Methods: Mice bearing Sarcoma-180 were randomly assigned to four groups: Ad Libitum (AL), Ad Libitum + Doxorubicin (ALDOX), Caloric Restriction (CR), and Caloric Restriction + Doxorubicin (CRDOX). Assessment included tumor weight and volume, food and caloric intake, hematotoxicity, lipid metabolism, oxidative stress and antioxidant markers, genotoxicity, morphological alterations in the tumor and liver, and overall survival. Results: The data obtained demonstrate that caloric restriction combined with doxorubicin is both safe and feasible, as it preserves body weight and does not induce metabolic disturbances. Importantly, this combined strategy produced a marked reduction in tumor volume and mass while also mitigating the hematotoxicity typically associated with doxorubicin. In peripheral blood, the regimen decreased chemotherapy-induced DNA damage, supporting a systemic protective effect. Consistently, the combination reduced oxidative stress markers (NOx and MDA) and enhanced antioxidant activity within the tumor. Histological analyses further confirmed these outcomes, showing tumor cell death with features compatible with apoptosis and reduced local invasion. Together, these data indicate that caloric restriction enhances the antitumor efficacy of doxorubicin while simultaneously improving treatment tolerance. Conclusions: This study demonstrates that caloric restriction, combined with doxorubicin, is safe, well-tolerated, and enhances the antitumor response in the Sarcoma-180 model. Full article

Polyomavirus-associated nephropathy was first reported over 50 years ago. However, it still represents a cause of renal injury in kidney transplant recipients, particularly in the first two years post-transplantation, with occurrence rates of 1–10%. The role played by immunosuppression in viral reactivation is well acknowledged, and the modulation of its level is the main strategy for clinical management. Viral and immunological evaluation are fundamental for optimizing its diagnostic and therapeutic pathway. In this review, the main features of BK polyomavirus and associated nephropathy in renal transplant patients are addressed and discussed from a virological point of view; the role of BK polyomavirus in hematopoietic stem cell transplantation and other solid-organ transplant patients is also briefly reported. Full article

It has been demonstrated that infants and young children exhibit immune tolerance as a consequence of immature immune systems, which are characterized by a natural Th2 bias. RSV infection has been reported to result in acute lower respiratory infection (ALRI), while formalin-inactivated vaccination has been observed to exacerbate Th2 responses, consequently leading to enhanced respiratory disease (ERD). Transcriptomic data from three independent cohorts of RSV-infected infants were analyzed (GSE246622 served as the discovery and train set; GSE105450 and GSE188427 were used as validation sets). Immune infiltration analysis revealed immunological characteristics, which were then used to perform unsupervised clustering using feature-related genes. WGCNA was used to identify co-expressed gene modules, while Mfuzz and TCseq were employed to analyze temporal expression patterns. Machine learning models were developed using a refined panel of candidate genes. Severe symptoms of RSV infection exhibited a strong correlation with age, with younger infants demonstrating more intense inflammatory responses from neutrophils, macrophages, mast cells and dendritic cells. A predictive model was constructed using ten co-expressed genes: The following genes were identified: MCEMP1, FCGR1B, ANXA3, FAM20A, CYSTM1, GYG1, ARG1, SLPI, BMX and SMPDL3A. It was observed that infants of a younger demographic demonstrated a heightened degree of immunosuppression and pronounced innate immune activation in patients of severe symptoms with RSV infection. However, eosinophils exhibited minimal involvement in these processes. These gene models pertaining to the neutrophil, macrophage or mast cell was found to be a relatively effective predictor in patients of severe symptoms. Full article

Background: Seronegative rheumatoid arthritis (SNRA), defined by the absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), represents 20–30% of rheumatoid arthritis cases. Once considered a milder phenotype, SNRA is now recognised as a heterogeneous entity in which a substantial subset of patients develops structural progression comparable to seropositive RA. The binary RF/ACPA-based definition is increasingly viewed as insufficient, as the broader anti-modified protein antibody (AMPA) family—including antibodies against carbamylated, acetylated and malondialdehyde–acetaldehyde–modified proteins—indicates that many “seronegative” patients may harbour unconventional humoral autoimmunity undetected by standard assays. Objectives: To synthesise contemporary insights into the epidemiology, immunopathology, diagnostic challenges and therapeutic management of SNRA, with emphasis on erosive versus non-erosive phenotypes and the implications of the AMPA paradigm. Methods: A comprehensive literature search of PubMed, Cochrane Library and Google Scholar identified randomised trials, observational cohorts and systematic reviews, with focus on studies published within the past decade. Results: SNRA displays partially distinct immune features, including lower formation of tertiary lymphoid structures and variable activation of innate inflammatory circuits. However, the traditional adaptive–versus–innate dichotomy is overly reductionist. Growing evidence suggests that unconventional humoral responses directed against non-classical post-translational modifications may be present in a proportion of RF/ACPA-negative patients. Additional qualitative dimensions—such as IgA isotypes and fine-specificity profiles—represent further heterogeneity with potential prognostic significance. Although ACPA remains the strongest predictor of erosive progression, up to one-third of seronegative patients develop erosions within five years. The 2010 ACR/EULAR criteria may delay diagnosis in SNRA. Cytokine inhibitors and JAK inhibitors show largely serostatus-independent efficacy, whereas B-cell and T-cell–targeted therapies demonstrate attenuated responses in SNRA. Conclusions: SNRA is clinically and immunologically diverse. Integrating the AMPA framework is essential for refining classification and prognostication. Distinguishing erosive from non-erosive forms may guide treatment, while future work should prioritise biomarkers predicting progression and therapeutic response. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis and immune dysregulation, with lung involvement being a major cause of morbidity and mortality. Type V collagen (COLV), a cryptic self-antigen, has been implicated in the pathogenesis of fibrosis in both SSc and lung allograft dysfunction. To characterize the early histological, molecular, and immunological events associated with lung remodeling following immunization with COLV in a murine model (IMU-COLV), and to establish a temporal framework for fibrosis progression. Using a time-course design, lung tissue from IMU-COLV mice was analyzed at multiple intervals post-immunization. Histopathological assessment, immunohistochemistry, and gene expression analysis were performed to evaluate inflammation, endothelial activation, extracellular matrix remodeling, and collagen composition. We observed a progressive and spatially organized pattern of lung remodeling, beginning with peribronchovascular immune infiltration and culminating in airway-centered fibrosis. These changes were accompanied by dynamic endothelial activation, increased expression of profibrotic markers, and alterations in collagen architecture particularly involving COLV. The remodeling pattern closely mirrors histological features observed in early SSc-associated interstitial lung disease and other fibrotic conditions, such as idiopathic pulmonary fibrosis and chronic lung allograft dysfunsion. The IMU-COLV model recapitulates key early features of SSc-related lung fibrosis, highlighting COLV’s potential role as a driver of immune-mediated tissue remodeling. These findings provide a valuable platform for investigating the mechanisms underlying fibrogenesis and for testing targeted interventions in the early phases of pulmonary fibrosis. Full article

Background: Chromobacterium violaceum is an emerging multidrug-resistant (MDR) Gram-negative bacterium associated with severe septicemia, abscess formation, and high mortality, particularly in immunocompromised individuals. Increasing antimicrobial resistance and the absence of approved vaccines underscore the urgent need for alternative preventive strategies. Traditional vaccine approaches are often inadequate against genetically diverse MDR pathogens, prompting the use of computational immunology and reverse vaccinology for vaccine design. Objectives: This study aimed to design and characterize a novel multi-epitope subunit vaccine (MEV) candidate against C. violaceum using a comprehensive pangenome-guided subtractive proteomics and immunoinformatics pipeline to identify conserved antigenic targets capable of eliciting strong immune responses. Methods: Comparative genomic analysis across eight C. violaceum strains identified 3144 core genes. Subtractive proteomics filtering yielded two essential, non-homologous, surface-accessible, and antigenic proteins—penicillin-binding protein 1A (Pbp1A) and organic solvent tolerance protein (LptD)—as vaccine targets. Cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes were predicted and integrated into a 272-amino-acid MEV construct adjuvanted with human β-defensin-4A using optimal linkers. The construct was evaluated through structural modeling, molecular docking with TLR4, molecular dynamics simulation, immune simulation, and in silico cloning into the pET-28a(+) vector. Results: The MEV construct exhibited strong antigenicity, non-allergenicity, and non-toxicity, with stable tertiary structure and favorable physicochemical properties. Docking and dynamics simulations demonstrated high binding affinity and stability with TLR4 (ΔG = −16.2 kcal/mol), while immune simulations predicted durable humoral and cellular immune responses with broad population coverage (≈89%). Codon optimization confirmed high expression potential in E. coli K12. Conclusions: The pangenome-guided immunoinformatics approach enabled the identification of conserved antigenic proteins and rational design of a promising multi-epitope vaccine candidate against MDR C. violaceum. The construct exhibits favorable immunogenic and structural features, supporting its potential for experimental validation and future development as a preventive immunotherapeutic against emerging MDR pathogens. Full article

Primary immune regulatory disorders (PIRDs) are a group of conditions characterised by a loss of immune tolerance. Two such disorders, CHAI and LATAIE, share common molecular mechanisms, leading to significant clinical overlap. Here, we report demographic, clinical, immunological, and molecular findings in 29 patients referred from different parts of India with a diagnosis of CHAI or LATAIE. LATAIE patients demonstrated a higher prevalence of consanguinity, while CHAI patients more often had a positive family history. Both disorders presented with overlapping clinical features, predominately autoimmune cytopenias, benign lymphoproliferation, and inflammatory bowel disease (IBD). However, the incidence of recurrent infections, otitis media, bronchiectasis, and hypogammaglobulinemia was higher among LATAIE patients as compared to CHAI. Flow cytometry analysis revealed significant differences in T cell subsets, particularly in percentages of CD4+ naïve cells and T regulatory cells (Treg), between the two disorders. B cell abnormalities were also observed. Molecular diagnosis was achieved using targeted or clinical exome sequencing, and specific protein expression was employed to validate the novel variants. Full article

Across the world, asthma is a prominent and widespread respiratory disorder that has a substantial clinical and socioeconomic influence. The classification of asthma subtypes should be performed precisely and effectively, with objectives such as personalized treatments, improved rehabilitation outcomes, and preventing tragic exacerbations. Typical screening approaches are primarily based on spirometry measures, immunologic assessments, and individual clinical diagnoses, and they are commonly affected by limitations such as uncertainty, crossover disparities, and restricted generalizability among various groups of patients. This study utilizes machine learning (ML) methodologies as a Data-Driven Approach (DDA)-based framework for asthma classification to overcome the mentioned challenges. Methodically constructed and evaluated classifiers, such as Random Forest and XGBoost, use the Asthma Disease Dataset from Kaggle, which consists of demographic data, lung function metrics (FEV1, FVC, FEV1/FVC ratio, and PEFR), and immunoglobulin E (IgE) biomarkers. A wide range of metrics such as accuracy, precision, recall, F1-score, receiver operating characteristic area under the curve (ROC-AUC), and average precision (AP) are used exhaustively to assess the performance of the model. The results indicate that though each model exhibits outstanding forecasting abilities, XGBoost has an enhanced classification capability, especially in recall and AP, which minimizes the proportion of false negatives, resulting in a clinically noteworthy result. The significance of the FEV1/FVC ratio, IgE levels, and PEFR as key indicators is recognized by feature interpretability analysis. These results emphasize the ability of ML-powered evaluation in advancing personalized healthcare and revolutionizing the clinical management of asthma. Full article

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by chronic, painful ulcerations. Despite increasing evidence suggesting immunological dysregulation, the role of IL-36 cytokines in PG remains poorly defined. To evaluate serum levels of IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38 in PG patients compared to healthy controls, and to assess their correlation with selected clinical parameters and cytokine ratios. 44 PG patients and 40 healthy controls were included in this case–control study. Serum cytokine levels were measured using ELISA. Correlations between cytokine levels and clinical features were analyzed using nonparametric tests. PG patients showed significantly lower serum levels of IL-36α and IL-36γ (p = 0.0003 and p = 0.02, respectively), with no difference in IL-36β. Conversely, levels of IL-36Ra, IL-37, and IL-38 were significantly higher in PG patients (p < 0.0001 for all). In the PG group, significant positive correlations were observed between IL-36α and IL-36β, and between IL-36β and IL-36γ, while IL-37 correlated negatively with IL-38. IL-36α was inversely associated with serum IgA levels and total ulcer surface area, and IL-36γ correlated negatively with white blood cell count. Our findings reveal a dysregulated IL-36 cytokine profile in pyoderma gangrenosum, marked by reduced serum levels of IL-36α and IL-36γ and elevated levels of IL-36Ra, IL-37, and IL-38. This may reflect a compensatory response to chronic inflammation. The inverse correlation between IL-36α and ulcer size suggests its potential involvement in wound healing. Despite lower serum levels of agonists, local biological activity of IL-36 cytokines may remain elevated due to tissue-level activation and consumption. These results highlight the therapeutic relevance of targeting the IL-36 pathway—particularly in treatment-resistant cases—and support further research into cytokine activity beyond serum concentration to guide novel therapeutic strategies. Full article