Search Results (6,416)

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Despite significant advances in graft survival, rejection continues to pose a major clinical challenge. Conventional monitoring tools, such as serum creatinine, donor-specific antibodies, and proteinuria, lack sensitivity and specificity for early detection of graft injury. Moreover, while biopsy remains the current gold standard for diagnosing rejection, it is prone to confounders, invasive, and associated with procedural risks. However, non-invasive novel biomarkers have emerged as promising alternatives for earlier rejection detection and improved immunosuppression management. This review focuses on the leading candidate biomarkers currently under clinical investigation, with an emphasis on their diagnostic performance, prognostic value, and potential to support personalised immunosuppressive strategies in kidney transplantation. Full article

Perfluoroalkyl substances (PFASs) possess immunosuppressive properties. However, their association with rheumatoid arthritis (RA) risk remains inconclusive across epidemiological studies. This study integrates population-based and mechanistic evidence to clarify the relationship between PFAS exposure and RA. We analyzed 8743 U.S. adults from the NHANES (2005–2018), assessing individual and mixed exposures to PFOA, PFOS, PFNA, and PFHxS using multivariable logistic regression, Bayesian kernel machine regression, quantile g-computation, and weighted quantile sum models. Network toxicology and molecular docking were utilized to identify core targets mediating immune disruption. The results showed that elevated PFOA (OR = 1.63, 95% CI: 1.41–1.89), PFOS (OR = 1.41, 1.25–1.58), and PFNA (OR = 1.40, 1.20–1.63) levels significantly increased RA risk. Mixture analyses indicated a positive joint effect (WQS OR = 1.06, 1.02–1.10; qgcomp OR = 1.26, 1.16–1.38), with PFOA as the primary contributor. Stratified analyses revealed stronger effects in females (PFOA Q4 OR = 3.75, 2.36–5.97) and older adults (≥60 years). Core targets included EGFR, SRC, TP53, and CTNNB1. PFAS mixtures increase RA risk, dominated by PFOA and modulated by sex/age. These findings help reconcile prior contradictions by identifying key molecular targets and vulnerable subpopulations, supporting regulatory attention to PFAS mixture exposure. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, largely due to its profound intratumoral heterogeneity and immunosuppressive microenvironment. Various classifications of GBM subtypes were created based on transcriptional and methylation profiles. This effort, followed by the development of new technology such as single-nuclei sequencing (snRNAseq) and spatial transcriptomics, led to a better understanding of the glioma cells’ plasticity and their ability to transition between diverse cellular states. GBM cells can mimic neurodevelopmental programs to resemble oligodendrocyte or neural progenitor behavior and hitchhike the local neuronal network to support their growth. The tumor microenvironment, especially under hypoxic conditions, drives the tumor cell clonal selection, which then reshapes the immune cells’ functions. These adaptations contribute to immune evasion by progressively disabling T cell and myeloid cell functions, ultimately establishing a highly immunosuppressive tumor milieu. This complex and metabolically constrained environment poses a major barrier to effective antitumor immunity and limits the success of conventional therapies. Understanding the dynamic interactions between glioma cells and their microenvironment is essential for the development of more effective immunotherapies and rational combination strategies aimed at overcoming resistance and improving patient outcomes. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Background: Toxoplasma gondii is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their metal complexes have shown promising activities against T. gondii. This study evaluated a gold (III) complex C3 and its TSC ligand C4 for safety in host immune cells and zebrafish embryos, followed by efficacy assessment in a murine model for chronic toxoplasmosis. Methods: The effects on viability and proliferation of murine splenocytes were determined using Alamar Blue assay and BrdU ELISA, and potential effects of the drugs on zebrafish (Danio rerio) embryos were detected through daily light microscopical inspection within the first 96 h of embryo development. The parasite burden in treated versus non-treated mice was measured by quantitative real-time PCR in the brain, eyes and the heart. Results: Neither compound showed immunosuppressive effects on the host immune cells but displayed dose-dependent toxicity on early zebrafish embryo development, suggesting that these compounds should not be applied in pregnant animals. In the murine model of chronic toxoplasmosis, C4 treatment significantly reduced the parasite load in the heart but not in the brain or eyes, while C3 did not have any impact on the parasite load. Conclusions: These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression. Full article

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article

Introduction: Medication adherence is essential for treatment and recovery following hematopoietic stem cell transplantation (HSCT). However, limited data exist on the most effective methods to measure adherence and the factors influencing it in HSCT patients. Materials and Methods: A prospective longitudinal study assessed immunosuppressant medication adherence in 150 patients with hematologic malignancies undergoing allogeneic HSCT. Adherence was assessed using pill counts, immunosuppressant medication levels, patient-reported medication logs, and the Medication Adherence Response Scale-5 (MARS-5) at 30, 100, and 180 days post-HSCT. We evaluated adherence rates, agreement between methods, and sociodemographic and clinical predictors. From patient-reported logs, we calculated dose adherence (comparing reported doses to expected doses) and timing adherence (comparing medication intake within ±3 h of the prescribed time). Kappa analysis assessed agreement among methods. Results: Of 190 eligible patients, 150 (78.9%) enrolled. The mean age was 57.5 years (SD = 13.5); 41.3% (n = 62) were female, 85.3% (n = 128) were non-Hispanic White, and 73.3% (n = 110) were married or living with a partner. Medication adherence varied across the three timepoints and by measurement type: 52–64% (pill counts), 18–24% (medication levels), 96–98% (medication log dose adherence), 83–84% (medication log timing adherence), and 97–98% (MARS−5). There was minimal agreement between measures (Kappa range: 0.008–0.12). Conclusions: Despite the feasibility of leveraging objective and patient-reported measures to assess medication adherence in HSCT patients, there was little agreement between these measures. Patient-reported measures showed high adherence, while objective measures like pill counts and medication levels revealed more modest adherence. The complexity of medication regimens likely contributes to this discrepancy. A rigorous approach to understanding medication adherence in the HSCT population may entail both objective and subjective measures of medication adherence. Full article

Antibody-mediated autoimmune diseases are common, can involve any organ system, and pose a large burden for patients and healthcare systems. Most antibody-mediated diseases are mediated by IgG antibodies. Selective targeting of pathogenic antibodies is an attractive treatment option which has already proven to be effective in antibody-positive generalized myasthenia gravis, maternal-fetal alloimmune cytopenias, and immune thrombocytopenic purpura. Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder mediated by pathogenic antibodies mainly of the IgG class with no approved therapy. Current treatment includes non-specific immunosuppression with corticosteroids, rituximab, and other immunosuppressive agents. With most therapies, time to response can be delayed and transfusions may be needed. Neonatal Fc receptor (FcRN) therapies provide rapid and sustained reduction of pathogenic IgG levels providing potential for fast, effective therapy in antibody-mediated autoimmune diseases including warm autoimmune hemolytic anemia. This review focuses on the emerging role of FcRn inhibition in autoimmune hematologic diseases, and their therapeutic potential in wAIHA. Full article

Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial–mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma. Full article

Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome. Full article

Protein-losing nephropathy (PLN) involves a heterogeneous group of pathologies leading to selective glomerular damage and development of renal disease. ICGN, the main cause of PLN, requires immunosuppressive treatment. However, the scientific evidence in veterinary medicine on immunosuppressive therapeutic schemes in this condition is limited. The aim of this study is to describe the clinical and paraclinical evolution of five dogs with PLN, presumably associated with ICGN, treated with chlorambucil as immunosuppressive monotherapy. Suspected IGCN was established by the presence of a urine protein–creatinine ratio (UPC) ≥ 3 without response to standard therapy, hypoalbuminemia < 2, or progressive azotemia. Patients were treated with a dosage range of chlorambucil from 0.16 to 0.4 mg/kg (mean 0.25 mg/kg) every 24 h as the sole immunosuppressant. In the end, 4/5 patients showed significant clinical improvement, 3/3 had resolution of the nephrotic syndrome, 5/5 had a sustained decrease in UPC values during follow-up and no relevant adverse effects were observed. In this report, chlorambucil proved to be a well-tolerated and potentially effective monotherapy for immune-mediated PLN in dogs. Full article