Hasil untuk "Immunologic diseases. Allergy"

J. Round, S. Mazmanian

Taku Okazaki, T. Honjo

A. Bousfiha, Abderrahmane Moundir, S. Tangye et al.

Shan Wang, Ge Peng, Alafate Abudouwanli et al.

The epidermal immune microenvironment is a multifaceted system in which the interplay between the skin microbiome and antimicrobial peptides plays a pivotal role in sustaining skin homeostasis and preventing dysbiosis. Disruption of these interactions can lead to inflammatory skin conditions such as atopic dermatitis. This review aims to explore the complex mechanisms by which antimicrobial peptides and the skin microbiome communicate within the epidermal immune microenvironment, emphasizing causal dynamics and the dual role of antimicrobial peptides. This analysis opens new avenues for targeted interventions, including antimicrobial peptide modulation and microbiome-based therapies, to restore skin health and mitigate inflammatory skin disorders.

Chao Lian, Chao Lian, Ling Liu et al.

Cancer immunotherapy has transformed oncology, yet its clinical efficacy is often limited by immune evasion within the tumor microenvironment (TME). Regulatory T cells (Tregs), a key immunosuppressive lineage, potently inhibit effector T-cell proliferation and activation, thereby dampening antitumor immune responses. Tregs are frequently enriched in diverse solid tumors, and their abundance correlates with poor prognosis, increased tumor invasiveness, and therapeutic resistance. A major mechanism driving this enrichment is the chemokine-chemokine receptor axis. Tumor cells, along with other stromal and immune cells in the TME, secrete chemokines including CCL22, CCL20, and CXCL12, which bind to CCR4, CCR6, and CXCR4 on Tregs and direct their recruitment and activation within the TME. This establishes an immunosuppressive niche that promotes tumor growth, facilitates metastasis, and reduces responsiveness to immunotherapy. This review consolidates eight experimentally validated chemokine-Treg axes from 2005 to 2025, with each study annotated by tumor type and represented by the highest observed level of evidence. A systematic representation illustrates how these axes mediate Treg-driven immunosuppression and maps their prevalence across cancers. Focusing on these axes provides mechanistic insights, highlights potential therapeutic targets, and identifies predictive biomarkers. Strategies targeting the chemokine-chemokine receptor axes, including selective receptor blockade, combination with immune checkpoint inhibitors, and omics-based approaches to resolve Treg heterogeneity, offer avenues to reprogram the immunosuppressive TME and enhance antitumor immunity.

Jérôme Lurel, Fadwa El Aissoug, Fatima-Zahra Hammoud et al.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting intertriginous regions, and emerging evidence suggests that systemic autoinflammation (“metainflammation”) contributes to its clinical heterogeneity. We report two cases of HS in patients of Moroccan origin with overlapping autoinflammatory features. The first case involves a 42-year-old man with HS since 2012, Hurley stage II, treated with adalimumab since 2019 and achieving an IHS4-70, who developed Behçet’s disease-like systemic manifestations in 2025; genetic testing revealed a heterozygous MEFV variant, and HLA typing included A02, A68, B15, B45, C02, and C06. The second case involves a 40-year-old man with HS since age 22, Hurley stage II, with persistent oral aphthosis; he achieved IHS4-70 on secukinumab in 2025 and responded to adjunctive colchicine for mucosal lesions, with HLA typing showing B18, B51, C07, and C15. These cases illustrate the interplay between HLA subtypes, autoinflammatory gene variants, and systemic inflammation in HS, highlighting a potential autoinflammatory HS subtype. Population-specific genetic factors, particularly in North African populations, may influence disease severity, systemic manifestations, and therapeutic response. Taken together, these observations support the concept that HS, in certain genetically predisposed individuals, may represent a systemic autoinflammatory/metainflammatory disease, underscoring the relevance of personalized therapeutic strategies.

Garazi Retegui, María Dolores Ugarte, Jaione Etxeberria et al.

To date, we have seen the emergence of a large literature on multivariate disease mapping. That is, incidence of (or mortality from) multiple diseases is recorded at the scale of areal units where incidence (mortality) across the diseases is expected to manifest dependence. The modeling involves a hierarchical structure: a Poisson model for disease counts (conditioning on the rates) at the first stage, and a specification of a function of the rates using spatial random effects at the second stage. These random effects are specified as a prior and introduce spatial smoothing to the rate (or risk) estimates. What we see in the literature is the amount of smoothing induced under a given prior across areal units compared with the observed/empirical risks. Our contribution here extends previous research on smoothing in univariate areal data models. Specifically, for three different choices of multivariate prior, we investigate both within prior smoothing according to hyperparameters and across prior smoothing. Its benefit to the user is to illuminate the expected nature of departure from perfect fit associated with these priors since model performance is not a question of goodness of fit. We propose both theoretical and empirical metrics for our investigation and illustrate with both simulated and real data.

K. Anagnostou, Sabita Islam, Y. King et al.

Summary Background Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts. Methods We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244. Findings The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant). Interpretation OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. Funding MRC-NIHR partnership.

N. Torow, T. Hand, M. Hornef

The mucosal immune system of neonates goes through successive, non-redundant phases that support the developmental needs of the infant and ultimately establish immune homeostasis. These phases are informed by environmental cues, including dietary and microbial stimuli, but also evolutionary developmental programming that functions independently of external stimuli. The immune response to exogenous stimuli is tightly regulated during early life; thresholds are set within this neonatal "window of opportunity" that govern how the immune system will respond to diet, the microbiota, and pathogenic microorganisms in the future. Thus, changes in early-life exposure, such as breastfeeding or environmental and microbial stimuli, influence immunological and metabolic homeostasis and the risk of developing diseases such as asthma/allergy and obesity.

Quanren Pan, Quanren Pan, Andrew F. Walls et al.

Aya K. H. Mahdy, Valentina Schöpfel, Gert Huppertz-Hauss et al.

IntroductionCrohn’s disease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have previously shown that the T cell repertoire of individuals with CD harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology.MethodsWe simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa of 27 treatment-naïve individuals with CD and 27 age-matched symptomatic controls.ResultsRegardless of disease status, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of individuals with CD relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells and an expansion of TRAV29/DV5-TRAJ5+ clonotypes in the blood repertoire of individuals with CD. Also, a significant depletion of multiple IGHV3-33-IGHJ4+ and IGHV3-33-IGHJ6+ clonotypes in the blood and gut IGH repertoire of individuals with CD.DiscussionOur findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues as not all disease-induced alterations will be detected in the blood.

Kunal Saxena, Amanda Dempsey, Rishi P. Verma et al.

This study explored attitudes/perceptions among parents who have not yet agreed to HPV vaccination for their 11–12-y-old children. US parents/guardians were recruited from a consumer panel for this online, cross-sectional survey. Parents (≥18 y) were eligible if their oldest child was 11–12, participated in their child’s vaccine decisions/visit, had not decided on, or would refuse the HPV vaccine, and understood English. Parents were excluded if their child had medical conditions affecting eligibility for HPV vaccination or if they declined to provide consent. Sampling quotas were used for parent and child age, sex, and US region. Of 200 participants, half were undecided whether to accept HPV vaccination for their children and half planned to refuse (purposely targeted recruitment). Most participants were women (70%) and White (86%) with a mean age of 39 y. Significantly, more parents who planned to refuse reported delaying/refusing other vaccinations compared to undecided parents (57% vs 11%, p < .001). Undecided parents selected significantly different primary reasons for not vaccinating (p < .001); they were more concerned about side effects (42% vs 25%) and less worried it would encourage their children to be sexually active (9% vs 22%). Most parents in the undecided cohort reported they would definitely have accepted the HPV vaccination (52% vs 36%) if their child’s provider had offered it when their child was younger, compared to parents who planned to refuse. Introducing HPV vaccine at an earlier age may be associated with increased parental acceptance specifically among those children who had not yet received HPV vaccination.

Wang X, Zhou N, Zhi Y

Xue Wang, Nan Zhou, Yuxiang Zhi Department of Allergy & Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Immunologic Diseases, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yuxiang Zhi, Email yuxiang_zhi@126.comAbstract: Cryopyrin-associated periodic syndrome (CAPS) is a rare autoinflammatory disorder often misdiagnosed as urticaria or urticarial vasculitis, thereby delaying treatment for patients. This report presents a large CAPS pedigree. The proband was a 57-year-old man with recurrent urticaria-like rash, fever, and arthralgia for more than 50 years and hearing loss for 28 years. Sixteen of his relatives had similar symptoms. One-generation sequencing revealed a c.778C>T; p.(Arg260Trp) variant in the NLRP3 gene, confirming the diagnosis of CAPS. The aim of this case report is to raise awareness of CAPS and its various clinical manifestations, highlighting that urticaria may be a presentation of autoinflammatory diseases, thereby improving diagnostic accuracy.Keywords: cryopyrin-associated periodic syndromes, case report, urticaria, large family

Srinivas Kanakala, Sneha Ningappa

Plant diseases pose a serious challenge to agriculture by reducing crop yield and affecting food quality. Early detection and classification of these diseases are essential for minimising losses and improving crop management practices. This study applies Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM) models to classify plant leaf diseases using a dataset containing 70,295 training images and 17,572 validation images across 38 disease classes. The CNN model was trained using the Adam optimiser with a learning rate of 0.0001 and categorical cross-entropy as the loss function. After 10 training epochs, the model achieved a training accuracy of 99.1% and a validation accuracy of 96.4%. The LSTM model reached a validation accuracy of 93.43%. Performance was evaluated using precision, recall, F1-score, and confusion matrix, confirming the reliability of the CNN-based approach. The results suggest that deep learning models, particularly CNN, enable an effective solution for accurate and scalable plant disease classification, supporting practical applications in agricultural monitoring.

Yang Liu

This paper conducts research on the established model and presents the main conclusions . Firstly, by separately considering the infectivity of each of the two infectious diseases and the infectivity of the population simultaneously infected with the two infectious diseases, the existence of three types of boundary equilibrium points is determined, as well as the existence of the interior equilibrium point when the parameters are under specific conditions. Then, the stability of the equilibrium points is analyzed. It is concluded that under different parameter conditions, the stability of the disease free equilibrium point can exhibit various scenarios, such as a stable node or a saddle-node, etc. For the boundary equilibrium points, the situation is more intricate,and a cusp may occur. The stability of the interior equilibrium point under specific conditions is also presented. Finally,the degeneracy of the equilibrium points is studied through the bifurcation theory.Mainly, the saddle-node bifurcation occurring at the interior equilibrium point is obtained, and when the infection rate of the first infectious disease, the infection rate of the second infectious disease, and the infection rate of the co-infected population to other populations are selected as bifurcation parameters, a codimension 3 B-T bifurcation is obtained.

Hongtao Hao, Joseph L. Austerweil

Chronic diseases often progress differently across patients. Rather than randomly varying, there are typically a small number of subtypes for how a disease progresses across patients. To capture this structured heterogeneity, the Subtype and Stage Inference Event-Based Model (SuStaIn) estimates the number of subtypes, the order of disease progression for each subtype, and assigns each patient to a subtype from primarily cross-sectional data. It has been widely applied to uncover the subtypes of many diseases and inform our understanding of them. But how robust is its performance? In this paper, we develop a principled Bayesian subtype variant of the event-based model (BEBMS) and compare its performance to SuStaIn in a variety of synthetic data experiments with varied levels of model misspecification. BEBMS substantially outperforms SuStaIn across ordering, staging, and subtype assignment tasks. Further, we apply BEBMS and SuStaIn to a real-world Alzheimer's data set. We find BEBMS has results that are more consistent with the scientific consensus of Alzheimer's disease progression than SuStaIn.

Bianca Olivieri, Fatma Esra Günaydın, J. Corren et al.

The development of monoclonal antibodies that selectively target IgE and type 2 immunity has opened new possibilities in the treatment of allergies. Although they have been used mainly as single therapies that have shown efficacy in the management of asthma and other T2-mediated diseases, there is a growing interest in using these monoclonal antibodies in combination with allergen immunotherapy (AIT). AIT has transformed the treatment of allergic diseases by aiming to modify the underlying immune response to allergens rather than just providing temporary symptom relief. Despite the proven efficacy and safety of AIT, unmet needs call for further research and innovation. Combination strategies involving biologics and AIT exhibit potential in improving short-term efficacy, reducing adverse events, and increasing immunological tolerance. Anti-IgE emerges as the most promising therapeutic strategy, not only enhancing AIT's safety and tolerability but also providing additional evidence of efficacy compared to AIT alone. Anti-IL-4 receptor offers a reduction in side effects and an improved immunological profile when combined with AIT, however its impact on short-term efficacy appears limited. The combination of cat dander subcutaneous immunotherapy with anti-TSLP was synergistic with enhanced efficacy and altered immune responses that persisted for one year after discontinuation compared to AIT alone. Long-term studies are needed to evaluate the sustained benefits and safety profiles of combination strategies.

Qian Wan, Zhongjin Xu, Xiaohui Liu et al.

BackgroundHepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition.Case PresentationA 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies.ConclusionThis study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.

Dongyun Rong, Yushen Su, Dechao Jia et al.

BackgroundSkin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.MethodsUtilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.ResultsWe identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.ConclusionThis study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.

Avneet Kaur, Rebecca Tyson, Iain Moyles

We analyze a disease transmission model that allows individuals to acquire fear and change their behaviour to reduce transmission. Fear is acquired through contact with infected individuals and through the influence of fearful individuals. We analyze the model in two limits: First, an Established Disease Limit (EDL), where the spread of the disease is much faster than the spread of fear, and second, a Novel Disease Limit (NDL), where the spread of the disease is comparable to that of fear. For the EDL, we show that the relative rate of fear acquisition to disease transmission controls the size of the fearful population at the end of a disease outbreak, and that the fear-induced contact reduction behaviour has very little impact on disease burden. Conversely, we show that in the NDL, disease burden can be controlled by fear-induced behaviour depending on the rate of fear loss. Specifically, fear-induced behaviour introduces a contact parameter $p$, which if too large prevents the contact reduction from effectively managing the epidemic. We analytically identify a critical prophylactic behaviour parameter $p=p_c$ where this happens leading to a discontinuity in epidemic prevalence. We show that this change in disease burden introduces delayed epidemic waves.