Search Results (1,119)

Background and Objectives: The average prevalence of sensitization to house dust mite in developed countries is more than 20%. The three major allergens of D. pteronyssinus—Der p 1, Der p 2, and Der p 23—have been associated with asthma severity. Allergen-specific immunotherapy (ASIT) is the only personalized and effective treatment that can change the natural course of allergic diseases such as allergic rhinitis or allergic asthma. Despite ASIT being an established treatment method, its effectiveness is still assessed using patient-reported outcome measures that determine quality of life, and there are no objective biomarkers that can accurately and reliably indicate the therapeutic efficacy of ASIT. This study aimed to monitor sensitization profiles to allergens, assess the effectiveness of ASIT, and evaluate total nasal symptom score (TNSS) and quality of life after six months of ASIT treatment. Materials and Methods: The molecular allergy diagnostic system was used to assess changes in patients’ sensitization profiles to allergens, and the validated questionnaires RQLQ and TNSS were used for quality-of-life assessment. Results: After 6 months of ASIT treatment against house dust mite allergens, a statistically significant increase in sIgE against the Der p 23 component was noted. In addition, a significant decrease in practical problems and an improvement in patients‘ emotional state were observed, while the TNSS score remained unchanged. Conclusions: Continuous monitoring of the Der p 23 component during further stages of ASIT is, therefore, essential to determine whether the observed changes reflect de novo sensitization or represent an immunological response to therapy. Full article

Introduction: Toxic Epidermal Necrolysis (TEN) and Steven–Johnson Syndrome (SJS) are rare yet dangerous dermatological emergencies presenting as necrosis of the skin and mucous membranes due to an immune reaction which may be associated with the use of pharmaceuticals—predominantly non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and antiretroviral drugs. During the postpartum period, women are administered numerous pharmaceuticals, including NSAIDs, analgesics, and antibiotics, due to pain and their susceptibility to infections, exposing them to potential adverse effects including allergies and immune reactions. Case Report and Review: The case reported here is a rare description of a patient in the early postpartum phase who presented with epidermal necrolysis whilst remaining hospitalized after a cesarean delivery. The multidisciplinary approach, early diagnosis, and treatment ensured the patient’s full recovery. Intravenous immunoglobulin treatment resulted in a rapid therapeutic effect. This literature review offers an insight into the epidemiology, diagnostic process, and treatment of this infrequent dermatological syndrome during the postpartum period. Results: Antibiotic treatment is a common culprit of TEN in this population; hence, clinicians should remain vigilant during antibiotic administration. Differential diagnosis with toxic shock syndrome is crucial, as TEN and SJS symptoms may mimic sepsis, which is a more common diagnosis in the postpartum period. Conclusions: The condition of the skin during the postpartum period should be closely monitored, as some systemic diseases may manifest abruptly as profound, postpartum hormonal changes affect the immunological response. Upon the discovery of suspicious skin lesions concomitant with systemic symptoms, an immediate multidisciplinary approach involving obstetricians and dermatologists is key to a rapid diagnosis and treatment to avoid maternal mortality. Full article

Oral candidiasis, mainly from Candida albicans, affects immunocompromised individuals, the elderly, and denture wearers. Probiotics offer immunomodulatory and microbiota-balancing benefits as potential antifungal alternatives. However, the comparative impact of different probiotic delivery methods remains inadequately explored. This systematic review evaluated the effectiveness of various probiotic delivery methods in reducing Candida colonization and clinical symptoms in oral candidiasis. Following PRISMA 2020 guidelines, a systematic review search across multiple databases included human clinical studies based (Medline, Web of Science, ScienceDirect, and ProQuest) on PICO criteria across all age groups. Outcomes assessed included Candida load, oral microbiota changes, symptom improvement, and disease recurrence. Of 297 articles screened, 10 met inclusion criteria. Delivery methods investigated included lozenges, capsules, yogurt, and cheese. Most studies reported reductions in Candida colony-forming units (CFUs) or prevalence, mainly for C. albicans and for non-albicans species, with probiotics such as Lactobacillus reuteri, L. rhamnosus, L. acidophilus, and Bifidobacterium strains. Some studies reported improved immunological markers, while symptom relief, especially when probiotics were combined with antifungals. Probiotics reduce Candida colonization and symptoms, with potential prolonged effects. They show promise as adjunctive therapies, but standardized, large-scale trials are needed for optimization. Full article

Background: Hypertensive conditions during pregnancy, such as preeclampsia (PE), are multisystem obstetric complications, accompanied by changes in the immunological status. Although several types of immune cells are involved in pathogenesis of preeclampsia, such as regulatory T cells, macrophages, natural killer cells, and neutrophils, most studies have focused on the concentration of circulating cytokines. Much less is known about intracellular cytokine production at the level of individual groups of peripheral blood immune cells. This gap limits our understanding of the early immunological changes that precede the clinical manifestation of the disease. Thus, the study of intracellular cytokine production in various leukocyte populations may provide new biomarkers for predicting preeclampsia. Objectives: To test the hypothesis that women with preeclampsia exhibit distinct intracellular cytokine profiles in specific peripheral blood immune cell subsets compared with normotensive pregnant women, and to assess whether these differences could serve as potential biomarkers for disease prediction. Methods: The study included a total of 78 pregnant women admitted to labor with physiological pregnancy (n = 32) and with gestational hypertension (GH) (n = 39) and PE (n = 7). The multicolor immunophenotyping with intracellular cytokine production of TNF, GM-CSF, IGF and receptor VEGFR-2 by different immunocompetent cell types was evaluated on a BD FACS CALIBUR flow cytometer. Results: Flow cytometry revealed a marked increase in the proportion of CD8⁺ GM-CSF⁺, CD56⁺VEGFR2⁺, CD14⁺IL-10⁺, and CD19⁺IGF⁺ cells in both hypertensive groups versus controls (p < 0.001). In contrast, CD56⁺TNF⁺ levels were significantly reduced (p < 0.001). For differentiating PE from GH, CD56+VEGFR2+ and CD19+IGF+ should be prioritized (AUC~0.66–0.78) with good specificity and moderate sensitivity. Conclusions: These data will not only expand existing knowledge about the role of intracellular cytokines in the pathogenesis of preeclampsia, but will also help to obtain new markers for predicting preeclampsia. Full article

Background/Objectives: Diet–microbiota interactions shape ageing; however, their sex-specific dimensions remain poorly defined. Human studies rarely stratify analyses by sex, while most evidence of sex-dependent microbial and metabolic responses comes from preclinical models. This review synthesizes current findings on the sex-specific pathways linking diet, microbiota, and healthy ageing. Methods: A narrative review was conducted by integrating human observational studies, randomized controlled trials, and mechanistic animal research. Evidence was organized into four domains: (1) age-related changes in gut microbial composition; (2) microbiota-derived metabolites; (3) dietary patterns and functional nutrients; and (4) sex-specific endocrine and immunometabolism interactions influenced by the gut microbiota. Results: Ageing is characterized by dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, expansion of Proteobacteria, and reduced production of key metabolites including butyrate, indoles, and polyamines. Dietary fiber, polyphenols, omega-3 fatty acids, and plant-based proteins help restore these pathways and mitigate inflammaging. Sex differences persist into later life: women show reduced estrobolome activity and SCFA decline after menopause, whereas men display higher levels of pro-atherogenic metabolites such as trimethylamine N-oxide (TMAO). Nutritional interventions, probiotics, and microbial metabolites exhibit sex-dependent responses in both human and animal studies. Conclusions: Diet–microbiota interactions shape ageing outcomes through sex-specific metabolic, hormonal, and immunological pathways. Incorporating sex as a biological variable is essential for developing personalized, nutrition-based strategies to support healthy ageing. Full article

Background and Objectives: MGN-3/Biobran (BRM4, Lentin Plus or Ribraxx) is a natural, rice bran-derived arabinoxylan immunoceutical that modulates the adaptive immune response to viral infections. In response to bacterial infections, basophils act as “first responders” and are also associated with modulation of the adaptive immune response. The maturation of pluripotent CD34⁺ stem cells into basophils is supported by the cytokine interleukin-3 (IL-3). The aim was to test the hypothesis that modulation of the adaptive immune response in bacterial infection by MGN-3/Biobran entails a basophilic response. The tick-related disorder Lyme borreliosis was chosen as the disease model; tick bites are associated with cutaneous IL-3-mediated basophil recruitment. Materials and Methods: A three-month randomised double-blind placebo-controlled trial was conducted in patients with a history of borreliosis who were suffering from symptoms attributable to this disorder. The immunoceutical group received oral Biobran; the dosage for both groups was 1 g thrice daily. Both groups were matched for age, sex, and ethnicity. Results: A higher percentage of basophil count occurred in the immunoceutical group (p = 0.038). The final general linear model included the group (immunoceutical/placebo) and change in fatigue assessed by the 11-item Chalder Fatigue Questionnaire (CFQ) (r² = 0.63; p = 0.0066). The change in basophil count was positively correlated with CFQ change (r_s = 0.633; p = 0.020); only the immunoceutical group showed a positive correlation. Conclusions: These results support the hypothesis being tested. Basophils may modulate the adaptive immune response by acting as immunoregulatory cells. They can regulate the functioning of type 2 T-helper lymphocytes, enhance immunological memory, and present antigens to CD8 T lymphocytes. Further studies are needed to clarify potential mechanistic factors and the timing of this basophilic response. Full article

Radiotherapy remains a central component of cancer therapy that induces DNA damage and cancer cell death. Beyond its cytotoxic effects, radiotherapy acts as a potent immunomodulator by releasing immunogenic molecules, inflammatory mediators, and neoantigens that shape anti-tumor immunity. Radiation-induced immune responses can have opposing effects, including immune activation or immunosuppression that dictate local tumor responses. Increasing evidence suggests these immunologic effects are not confined to the site of irradiation, as radiation exposure to surrounding normal tissue can trigger systemic immune signaling that affects local tumor progression as well as metastatic spread. This review examines radiotherapy-induced immune responses across three interconnected contexts: (i) tumor-intrinsic signaling during radiation; (ii) tumor microenvironmental changes where innate and adaptive immune responses alter local outcomes; and (iii) systemic and off-target effects contributing to broader immune remodeling. A comprehensive understanding of radiotherapy-induced immune responses will guide therapeutic strategies to enhance its immunological potential while minimizing unintended immune and off-target effects. Full article

Peripheral blood serves both as a source of effector immune cells that migrate to exocrine glands and as a reflection of the immunological changes occurring in patients with Sjögren’s disease (SjD). These changes may be linked to the clinical state of these patients. We analyzed total cell counts in the peripheral blood, as well as frequencies of individual leukocyte subpopulations, membrane expression levels of CD38 and CD157, and serum concentrations of soluble sCD38 and sCD157 in SjD patients (n = 40) and age-matched healthy controls (n = 20). Hierarchical clustering based on the cell count of leukocyte subpopulations was employed to identify distinct patient subgroups. Associations between these clusters and clinical parameters were subsequently evaluated. Key findings included a reduction in lymphocyte counts and their subpopulations, alongside increased CD38 expression on CD38⁺ B cells (p = 0.047) and, unexpectedly, on monocytes (p = 0.014) when comparing patients and controls. The involvement of innate immunity was further supported by the differential expression of CD157 across patient samples. Patients with low cell counts exhibited reduced CD157 expression on monocytes and granulocytes (p < 0.02), tested positive for anti-Ro antibodies, and reported severe fatigue. Our findings suggest that innate immune cells, such as monocytes and granulocytes in peripheral blood, are also likely to contribute to the manifestation and progression of SjD. The differential expression of CD157 may reflect distinct immunopathological states and warrants further investigation, as its precise role in exocrine gland involvement and extra-glandular manifestations lies beyond the scope of this study. Full article

Diagnosis and prognosis of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) spectrum remain largely dependent on clinical assessments due to a lack of established fluid biomarkers. While neurofilaments and the cerebrospinal fluid (CSF) phosphorylated-tau/total-tau ratio (pTau:tTau) have been studied, their limitations, including their lack of clinical implementation and low specificity, necessitate multimodal approaches. This study aimed to characterize the biological features of the ALS/FTD spectrum through integration of clinically available parameters. We conducted a retrospective, single-center, cross-sectional study analyzing routinely collected clinical, neuroimaging, CSF, and serum data from 229 samples, including 45 from patients with ALS, 26 from patients with FTD, 158 from patients with other neurodegenerative diseases, and 29 from cognitively healthy controls. We implemented propensity score-weighted comparisons, an F1 score-based optimal cut-point determination for the pTau:tTau ratio, and a regularized XGBoost-based multimodal feature modeling approach. The biomarker and model performance was evaluated by the area under the precision–recall curve (AUC-PR). Feature importance analysis identified characteristic indicators of the ALS/FTD spectrum. Consistent with the prior literature, the pTau:tTau ratio was significantly reduced in ALS/FTD, but the classification performance was modest (AUC-PR 0.32). A multimodal model integrating clinical, biofluid, and neuroimaging features achieved a notably better performance (AUC-PR 0.75). Feature importance analysis revealed an ALS/FTD signature beyond the pTau:tTau ratio characterized by higher global cognition, younger age, an altered Aβ42/pTau ratio, and immunoglobulin changes (CSF IgG:IgA, serum IgG). Integration of clinical routine data centered on tau, amyloid, and immunological pathophysiology as well as temporal disease dynamics provide a contextualized biological characterization of the ALS/FTD spectrum. This approach offers a foundation for hypothesis generation regarding ALS/FTD pathophysiology and biomarker-supported diagnosis. Full article

Primary glomerulopathies share common immune dysregulation but differ in their predominant pathways. We compared immune checkpoint profiles in minimal change disease (MCD) and membranous nephropathy (MN) with those in healthy volunteers (HV). In a cohort of 90 individuals (MCD, n = 30; MN, n = 30; HV, n = 30), we performed multiparameter flow cytometry of PBMCs to assess the expression of PD-1/PD-L1, CTLA-4/CD86, and CD200/CD200R on CD4+and CD8+ T cells, CD19+ B cells, and natural killer cells (NK cells). ELISA measured serum soluble checkpoint concentrations, and transcript levels in PBMCs were measured by qPCR. Nonparametric statistics and ROC analysis were used. In MCD, a skewed T cell pattern was observed, characterized by dominant expression of PD-1 and CTLA-4, whereas in MN, a humoral predominance was observed with higher PD-L1 expression and attenuated CD200/CD200R axis. Across diseases, expression profiles and correlations between markers differed between HV and between MCD and MN. Soluble checkpoints (sPD-1, sPD-L1, sCD200, sCD200R) showed potential discriminatory value for GN compared to HV and for differentiating MCD from MN in ROC analyses. These findings indicate that the mechanisms maintaining immune tolerance in primary GN are standard but pathway-specific, consistent with the dominant immunological component of each disease. A significant implication of this study is the need to conduct tissue-level studies to confirm clinical utility and provide insights into personalized immunomodulatory strategies targeting PD-1/PD-L1, CTLA-4/CD86, and CD200/CD200R. Full article

Background and Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder primarily affecting children, driven by genetic, immunologic, and environmental factors. Emerging evidence links gut microbiota alterations to immune modulation and AD severity. Probiotics, live microorganisms providing health benefits when consumed in adequate amounts, have been proposed as a potential adjunctive therapy. This review evaluates the efficacy of various probiotic treatments in reducing SCORAD indices and symptoms in children with AD, and its effects on immunologic markers such as IgE. Materials and Methods: Through a systematic literature review of multiple electronic databases through 9 October 2024, we identified randomized controlled trials (RCTs) in pediatric patients with an established diagnosis of atopic dermatitis. Our search strategy was as follows: “((atopy) OR (dermatitis) OR (hypersensitivity)) AND pediatric AND probiotic” yielding 25 total studies. Patients were treated with either a probiotic regimen or placebo and assessed for levels of IgE and SCORAD indices. Results: Of 25 studies extracted, 14 RCTs evaluated the effects of probiotics on atopic dermatitis using SCORAD scores. Eleven showed significant reductions in SCORAD indices. Pooled analysis using a random-effects model (Hedges’ g ≈ 0.65, p < 0.05) indicated a moderate to large improvement in AD severity with probiotic therapy. However, heterogeneity in probiotic strains, intervention duration, and limited sample sizes are limitations that warrant further investigation. Secondary analysis of IgE changes showed a non-significant effect (g ≈ 0.15, p = 0.13), possibly due to short study durations (mean 12 weeks). Conclusions: Probiotics demonstrate a moderate to large clinical impact in reducing SCORAD indices among children with atopic dermatitis. These findings highlight their potential as a future adjunctive, non-pharmaceutical therapy for the roughly 9.6 million pediatric patients affected in the United States. Further studies are needed to clarify strain-specific effects and patient factors influencing response. Full article

Depression and obesity are amongst the most serious global health challenges. Each of them is associated with high morbidity, chronicity, and socioeconomic burden. Increasing evidence suggests that these conditions are not merely comorbid but share convergent biological pathways (e.g., hypothalamic–pituitary–adrenal axis dysregulation, chronic inflammation, gut dysbiosis, and mitochondrial dysfunction). All these components contribute together to the development and persistence of depressive symptoms as well as to an increase in adiposity. Within this framework, adipose tissue has emerged as an essential endocrine organ that has a deep impact on neuroimmune signalling and mood regulation through its secreted molecules, such as leptin, adiponectin, resistin, omentin, apelin, chemerin, and visfatin. The current management of depression involves a comprehensive, multidisciplinary approach that includes pharmacological treatment and psychotherapeutic support, alongside lifestyle changes. Here we highlight the molecular crosstalk between adipose tissue and the brain, summarising the evidence of adipokines’ dysregulation role in connecting metabolic dysfunction to depressive neurobiology. By integrating metabolic, immunological, and neuroendocrine perspectives, this narrative review underscores the need to reconceptualise depression as an immunometabolic disorder. Understanding adipokine-mediated pathways may reveal new biomarkers and therapeutic targets, fostering interdisciplinary approaches. This would allow for the development of new treatment strategies, which include recombinant adipokines, anti-inflammatory agents, and microbial modulation. These new strategies might provide a significant benefit in selected patients, in addition to conventional antidepressants. Full article

Agriculture is still at serious risk from viral infections, particularly in light of climate change and more intensive farming practices. Small non-coding RNAs (sRNAs), in particular microRNAs (miRNAs) and circular RNAs (circRNAs), have emerged as crucial post-transcriptional regulators of plant antiviral defense in this setting. These molecules provide an essential RNA-based immunity layer by regulating hormones, autophagy, redox balance, immunological signaling, and programmed cell death. In this work, we examine the molecular processes through which circRNAs and miRNAs function during viral infection, focusing on how they affect autophagy and systemic acquired resistance (SAR). Through thorough searches of PubMed, Web of Science, and Scopus, we combined findings from peer-reviewed experimental and transcriptomic studies. Our study covers important crops as well as model species (Arabidopsis thaliana, Nicotiana benthamiana), providing a thorough understanding of sRNA synthesis, target control, and antiviral signaling. By combining previously disparate data, this review provides a coherent framework for understanding how short RNAs affect plant immune responses to viral infections. We highlight key regulatory relationships that need further study and propose that these results can be used as a foundation for new RNA-based biotechnological approaches. By carefully altering RNA regulatory mechanisms, scientists can use this information to help them create more resistant crops. Full article

The controlled pro-inflammatory immune response is critical for fighting against external and endogenous threats, such as microbes/pathogens, allergens, xenobiotics, various antigens, and dying host cells and their mediators (DNA, RNA, and nuclear proteins) released into the circulation and cytosol (PAMPs, MAMPs, and DAMPs). Several pattern recognition receptors (PRRs) and their downstream adaptor molecules, expressed by innate and adaptive immune cells, are critical in generating the inflammatory immune response by recognizing PAMPs, MAMPs, and DAMPs. However, their dysregulation may predispose the host to develop inflammation-associated organ damage, neurodegeneration, autoimmunity, cancer, and even death due to the absence of the inflammation resolution phase. The cytosolic calcium (Ca²⁺) level regulates the survival, proliferation, and immunological functions of immune cells. Cysteine-rich proteases, specifically calpains, are Ca²⁺-dependent proteases that become activated during inflammatory conditions, playing a critical role in the inflammatory process and associated organ damage. Therefore, this article discusses the expression and function of calpain-1 and calpain-2 (ubiquitous calpains) in various innate (epithelial, endothelial, dendritic, mast, and NK cells, as well as macrophages) and adaptive (T and B cells) immune cells, affecting inflammation and immune regulation. As inflammatory diseases are on the rise due to several factors, such as environment, lifestyle, and an aging population, we must not just investigate but strive for a deeper understanding of the inflammation and immunoregulation under the calpain system (calpain-1 and calpain-2 and their endogenous negative regulator calpastatin) lens, which is ubiquitous and senses cytosolic Ca²⁺ changes to impact immune response. Full article