Allergic diseases, including asthma, allergic rhinitis (AR), and atopic dermatitis (AD) frequently co-occur with psychiatric disorders such as depression, anxiety, and Autism spectrum disorder (ASD), reflecting their frequent co-occurrence and shared biological pathways. The etiology of these comorbidities is multifactorial, involving genetic, environmental, psychological, and immunological factors and their dynamic interactions. Both disease groups are characterized by chronic inflammation, immune dysregulation, and neuroimmune cross-talk, while epigenetic modifications, hypothalamic–pituitary–adrenal (HPA) axis dysfunction, and microbiota–gut–brain interactions have emerged as key mechanistic links. This convergence of immune and neural pathways suggests that allergic and psychiatric disorders may arise from common molecular and cellular processes rather than independent disease entities. Understanding these shared mechanisms may facilitate the development of integrated diagnostic and therapeutic strategies for allergic and psychiatric comorbidities. The rising global burden of allergy-psychiatry comorbidities underscores the urgent need for precision strategies that move beyond symptom management toward mechanistically informed interventions. Recent advances in multi-omics profiling, nanotechnology, and wearable biosensors offer unprecedented opportunities for early detection, real-time monitoring, and personalized treatment. In particular, nano-enabled biosensors capable of tracking neuroimmune biomarkers represent a transformative step in bridging immune, neurological, and mental health domains. By linking shared pathogenesis with technological innovation, this review highlights the critical importance of interdisciplinary research at the intersection of neuroimmunology, psychiatry, and biomedical engineering. Such approaches have the potential to redefine diagnostics and therapeutics for allergy-psychiatry comorbidities, improving clinical outcomes, reducing healthcare burden, and advancing patient-centered care.
Dupilumab is a human monoclonal antibody targeting the IL-4 receptor alpha subunit, thereby inhibiting both IL-4 and IL-13 signaling pathways central to type 2 inflammation. Since its initial approval for atopic dermatitis in 2017, dupilumab has gained multiple FDA-approved indications across allergic and eosinophilic diseases, including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, chronic obstructive pulmonary disease with type 2 inflammation, bullous pemphigoid, and allergic fungal rhinosinusitis. This review summarizes the immunologic mechanisms, pharmacologic properties, clinical efficacy, biomarker effects, and safety profile of dupilumab across approved indications, while also discussing its role within the broader landscape of type 2 biologics. Landmark clinical trials consistently demonstrate significant reductions in disease severity, exacerbation frequency, corticosteroid dependence, and symptom burden, with improvements in quality of life across multiple organ systems. Biomarker studies show suppression of type 2 inflammatory mediators, including thymus activation-regulated chemokine (TARC), eotaxin-3, FeNO, and IgE, although eosinophil dynamics vary among diseases. Dupilumab has generally demonstrated a favorable long-term safety profile, with conjunctivitis and transient eosinophilia representing the most commonly recognized adverse events. Emerging evidence also supports potential roles in biomarker-guided precision therapy, disease modification, and combination biologic strategies. Given its efficacy across multiple indications and expanding indications, dupilumab has become an important therapeutic option for patients with overlapping type 2 inflammatory comorbidities and continues to reshape the management of allergic and eosinophilic diseases.
The field of allergy and immunology is undergoing a paradigm shift from phenotype-based disease classification toward precision immunology driven by mechanistic understanding, systems biology, and targeted therapeutics. Advances in developmental immunology, epithelial barrier biology, microbiome science, neuroimmune interactions, and translational immunotherapy have revealed the complex and interconnected nature of immune-mediated diseases across the lifespan. Early-life immune programming is increasingly recognized as a critical determinant of allergic disease susceptibility, highlighting opportunities for preventive intervention through modulation of barrier integrity, microbial exposure, nutrition, and immune tolerance. Simultaneously, the emergence of endotype-guided management strategies has transformed the treatment landscape of airway and allergic diseases, particularly through the integration of biomarkers and biologic agents targeting specific inflammatory pathways. Beyond classical allergic disorders, growing evidence supports a systems-level interaction between environmental exposures, gut microbiota, metabolic factors, and neuroimmune signaling in sustaining chronic inflammation and immune dysregulation. In parallel, modern vaccinology and autoimmune therapeutics are evolving toward personalized approaches that incorporate host immune heterogeneity, predictive biomarkers, and computational modeling. Collectively, these developments are redefining allergy and immunology as an integrated discipline centered on precision prevention, individualized treatment, and restoration of immune tolerance. This White Paper of the 2026 CLIMAX symposium synthesizes emerging concepts across early-life immunity, precision airway medicine, neuroimmune crosstalk, vaccinology, and autoimmunity, while discussing translational challenges, future therapeutic directions, and the growing role of systems immunology and artificial intelligence in shaping next-generation personalized immune care.
Background Remibrutinib has recently become available for the clinical management of chronic spontaneous urticaria (CSU) in China, yet relevant clinical experience remains limited, highlighting an urgent demand for population-specific real-world evidence. We therefore evaluated the early effectiveness, safety and clinical utilization of remibrutinib in a heterogeneous Chinese outpatient cohort. Methods This interim analysis was conducted based on an ongoing prospective, multicenter observational cohort enrolling 32 adult patients with CSU receiving treatment in routine outpatient settings. Eligibility criteria did not restrict prior treatment regimens, nor did it limit physician-managed background or rescue therapies for CSU. The safety set consisted of 29 patients who received at least one dose of remibrutinib, and the Week 4 efficacy set comprised 25 patients with evaluable 7-day Urticaria Activity Score (UAS7) data. Assessed outcomes included UAS7, Urticaria Control Test (UCT), Dermatology Life Quality Index (DLQI), 7-day Angioedema Activity Score (AAS7), Angioedema Control Test (AECT), treatment patterns and adverse events. All analyses were descriptive. Baseline UAS7 > 6 was defined as failure to achieve well-controlled disease. Results At remibrutinib initiation, 22 of 27 patients (81.5%) with available baseline UAS7 had not achieved well-controlled disease. Baseline exposure to H1-antihistamines, omalizumab, and systemic corticosteroids was documented in 21 of 29 (72.4%), 19 of 29 (65.5%), and 12 of 29 patients (41.4%), respectively; 20 of 29 (69.0%) had exposure to at least two baseline CSU treatment classes. Two patients (6.9%) initiated remibrutinib after H1-antihistamines as their only documented baseline CSU drug class, and both had baseline UAS7 > 6. At Week 4, mean UAS7 decreased from 19.4 (95% confidence interval [CI], 14.20-24.68) to 5.3 (95% CI, 2.70-7.86). Nineteen of 25 patients (76%) had UAS7 ≤ 6, and 9 of 25 (36%) had UAS7 = 0. Mean UCT increased from 6.36 to 11.56 (P < 0.001), and mean DLQI decreased from 8.56 to 3.24 (P = 0.012). Among four patients with paired angioedema assessments, AAS7 decreased from 44.5 at baseline to 0 at Week 4, while median AECT increased from 3.0 to 16.0. These findings were exploratory because paired observations were limited. Ten of 29 patients (34.5%) reported at least one adverse event (AE); no serious or severe AEs occurred. Petechiae were recorded in 4 of 29 patients (13.8%). Conclusions Across patients with diverse baseline treatment exposures, remibrutinib was associated with rapid improvements in disease activity, disease control, and quality of life by Week 4. However, longer-term follow-up is necessary to assess the durability of these improvements and further characterize the safety profile of remibrutinib. (Chinese Clinical Trial Registry number: ChiCTR2600127540.)
The integration of LLMs as well as multimodal artificial intelligence (AI) into allergy clinics signifies a paradigm shift in treatment personalization, diagnostic precision, and clinical workflow optimization. Even as these technologies exhibit remarkable potential for recognizing complex allergic phenotypes, heading severe reactions, and optimizing allergen immunotherapy, notable challenges persist concerning diagnostic accuracy, patient privacy, regulatory compliance, and algorithmic transparency. This review scrutinizes current clinical applications, implementation barriers, diagnostic performance metrics, and regulatory frameworks governing LLM and multimodal AI deployment in allergology. The review highlights that although AI copilots can significantly enhance allergists’ clinical reasoning as well as efficiency, their optimal benefits require multi-stakeholder collaboration on transparency, validation, equity, and governance.
Background Influenza vaccination remains the most effective strategy for preventing severe influenza-related morbidity and mortality. However, individuals with allergic diseases or immune dysregulation exhibit altered immune responses to vaccination due to underlying immune dysfunction, immunosuppressive therapies, or inherent Th2-biased inflammatory milieus. Purpose of review This review synthesizes current evidence on the immunological mechanisms, safety, and efficacy of influenza vaccination in populations with allergic and immune-mediated disorders. Recent findings Studies demonstrate that inactivated influenza vaccines are generally safe across allergic and immunocompromised populations, with no increased risk of disease flares or allergic exacerbations. However, vaccine immunogenicity shows selective attenuation in specific patients receiving methotrexate, anti-CD20 therapies, or high-dose corticosteroids exhibit significantly impaired seroconversion, while newer biologic agents including anti-IgE, anti-IL-4/IL-13, anti-IL-5, JAK inhibitors therapies have minimal impact on vaccine responses. While individuals with poorly controlled atopic dermatitis demonstrate reduced Th1-type cellular responses and shorter antibody persistence, though most still achieve clinically adequate seroprotection rates. Enhanced strategies such as high-dose and adjuvanted vaccines can further improve immune responses in immunocompromised individuals and high-risk atopic patients. Conclusion Influenza vaccination is safe and strongly recommended for individuals with allergic and immunologically mediated conditions. Evidence-based strategies—including enhanced vaccine formulations, optimized timing, and adherence to updated food allergy guidelines—can maximize protection in these vulnerable populations. Future research should focus on personalized vaccinology approaches, novel platforms, and public health strategies to optimize both individual protection and herd immunity benefits.
Background Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder, clinically manifested as recurrent localized edema of the skin and mucous membranes, which can involve the gastrointestinal tract and cause severe abdominal pain when present. It is often misdiagnosed as gastroenteritis or allergic diseases. Objective To report a case of a patient with long-term misdiagnosis of HAE and the family situation, in order to enhance the clinical understanding of this disease. Method The patient's medical history and family history were collected, and laboratory tests were conducted, including the determination of complement C4, C1 esterase inhibitor (C1-INH) concentration and function. Result The patient was a 39-year-old female who had recurrent skin and mucous membrane edema accompanied by abdominal pain for 9 years. She had been misdiagnosed as gastroenteritis and allergy. Ten members of the family had similar attack histories. Laboratory tests showed that Complement C4: 0.01g/L (normal range 0.1-0.4g/L).C1-INH concentration(nephelometry): <0.03g/L (normal range 0.21-0.39g/L).C1-INH function test(ELISA): 1.7% (normal range ≥68.0%).Based on typical clinical manifestations, family history, and significantly reduced C1-INH concentration and function, the final diagnosis was HAE-1 type. Conclusion For unexplained episodic edema, especially when there is a family aggregation history, early detection of C4, C1-INH concentration and function should be conducted to make a clear diagnosis. This case emphasizes the importance of including HAE in the differential diagnosis of recurrent abdominal pain and edema to reduce misdiagnosis and improve patient prognosis.
Artificial intelligence revolutionizes food and drug allergy care. In food allergy, it predicts risks via microbiome/IgE data, diagnoses via multi-modal analytics, optimizes therapies (OIT), and manages allergens (biosensors, hypoallergenic products). For drug allergy, AI predicts hypersensitivity (β-lactam risk), diagnoses via EHR NLP, explores therapeutic targets, and streamlines management (ADR classification, anaphylaxis surveillance). Despite progress, gaps remain: underrepresented population models, immunocompromised diagnosis, and global data standardization. AI drives precision in allergy prediction, diagnosis, therapy, and management, but needs refinement to fully address clinical complexity. This review highlights how artificial intelligence is transforming the landscape of food and drug allergy research, from early risk prediction to personalized management, while also addressing the current limitations and future opportunities.
Childhood obesity-related asthma is a distinct and increasingly prevalent phenotype, associated with greater symptom burden, poorer disease control, frequent exacerbations, and reduced responsiveness to standard therapy. This phenotype is complex and heterogeneous, with underlying mechanisms involving airway inflammation, adipokine imbalance, metabolic dysregulation, changes in the gut microbiome, and altered respiratory mechanics. Current treatment for these children remains challenging, as they often show reduced responsiveness to standard inhaled corticosteroids. Multidisciplinary strategies including weight reduction, lifestyle interventions, and careful management of comorbidities are therefore essential. Emerging evidence suggests potential roles for metabolic drugs, biologic therapies, and microbiota-targeted interventions, although pediatric-specific data are still limited. Therefore, in this review, we summarize the epidemiology, pathogenesis, clinical features, and management of obesity-related asthma in children. We also highlight important gaps in knowledge and emphasize the need for large-scale, pediatric-focused, multicenter studies to develop effective, phenotype-specific treatment strategies for this growing and vulnerable patient population.
Allergic rhinitis (AR) is a prevalent chronic inflammatory disorder that significantly impairs quality of life worldwide. In 2024, the World Federation of Chinese Medicine Societies (WFCMS) released the International Clinical Practice Guidelines of Chinese Medicine: Allergic Rhinitis (SCM 80–2024), the first globally standardized evidence-based clinical practice guidelines for comprehensive TCM management of AR.Developed through a transparent, prospectively registered process on the PREPARE platform (Registration No. 2023CN081), the guidelines synthesized data from 351 randomized controlled trials involving 43,276 patients and applied the GRADE-TCM framework, which integrates four categories of TCM-specific evidence. 32 recommendations were established through five rounds of Delphi consensus, covering four major TCM syndromes and both internal and external therapeutic interventions.This article presents the English interpretation of the guidelines. Beyond summarizing the core recommendations, it focuses on the methodological innovations underpinning the guidelines, the epistemological distinctions between Chinese and Western medical paradigms, and the regulatory and practical challenges associated with its implementation in predominantly Western healthcare contexts.
Background Allergic rhinitis (AR) is a prevalent IgE-mediated inflammatory disease characterized by nasal symptoms and elevated inflammatory biomarkers in nasal secretions. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase (TPS) are key mediators of AR pathogenesis, but their dynamic changes post-treatment remains underexplored. Objective This study aimed to evaluate the effects of standard pharmacotherapy (fluticasone propionate nasal spray + fexofenadine hydrochloride) on nasal secretion levels of ECP, MPO, and TPS in AR patients and assess their diagnostic and prognostic utility. Methods A total of 34 moderate to severe dust mite-sensitized AR patients and 20 healthy controls were enrolled. Nasal secretions were collected before and after 2 weeks of treatment. Biomarker concentrations (ECP, MPO, TPS) were measured using magnetic particle detection (MPD), and eosinophil percentages (EOS%) were analyzed via cytology smears. Statistical analyses included Mann-Whitney U tests and ROC curve evaluation. Results Post-treatment, AR patients showed significant reductions in ECP (5.95 ± 2.85 vs. 3.21 ± 1.82 ln (AU/μl), p < 0.001) and TPS (5.34 ± 2.02 vs. 3.31 ± 2.21 ln (AU/μl), p < 0.001), with ECP normalizing to HC levels (2.10 ± 0.84 ln (AU/μl)). TPS remained elevated compared to HC (−0.55 ± 0.99 ln (AU/μl), p < 0.05), while MPO levels were unchanged (143.2 ± 160.6 vs. 175.9 ± 174.8 AU/μl) but lower than HC (289.0 ± 105.1 AU/μl, p < 0.01). ROC analysis revealed high diagnostic accuracy for TPS (AUC = 0.959) and combined biomarkers (AUC = 0.974) in distinguishing AR from HC, while ECP correlated best with symptom severity (AUC = 0.819). Conclusion Standard AR therapy effectively reduces ECP and TPS levels, with ECP serving as a sensitive marker for treatment response and TPS for early diagnosis. Persistent post-treatment TPS elevation suggests unresolved mast cell activation, highlighting the need for optimized therapies. Noninvasive nasal secretion analysis offers a reliable tool for monitoring AR inflammation.
Allergic asthma (AA) is driven by persistent Th2 inflammation, but the mechanisms underlying the survival of pathogenic CD4+ T cells remain unclear. Myeloid cell leukemia-1 (Mcl-1), a pro-survival Bcl-2 family protein, and lysine demethylase 4D (KDM4D)-mediated epigenetic regulation are emerging as key factors in cell survival and inflammation, yet their role in AA pathogenesis has not been fully elucidated. This study aimed to investigate the functional role and epigenetic regulation of the KDM4D-Mcl-1 axis in CD4+ T cell apoptosis resistance and Th2 polarization in AA, and to explore its potential as a therapeutic target. Here we report that in murine AA models, CD4+ T cells showed 2.8-fold higher Mcl1 mRNA expression and marked apoptosis resistance (68.7 % vs. 32.4 % cisplatin-induced death in naive controls, p < 0.001), which correlated strongly with disease severity. Mechanistically, KDM4D mediated H3K9me3 demethylation at the Mcl1 promoter, leading to 58 % hypomethylation (p < 0.01), 40 % reduced H3K9me3 occupancy, and 2.1-fold increased RNA polymerase II recruitment. CD4+ T cell-specific Kdm4d ablation restored apoptosis sensitivity (65.3 % vs. 31.2 % cell death in wild-type AA mice, p < 0.001) and reduced Th2 polarization (IL-4+CD4+ cells: 6.1 % vs. 18.4 %, p < 0.001). Clinically, KDM4D was overexpressed 3.2-fold in AA patients (p < 0.01) and correlated with serum IgE levels (r = 0.71, p = 0.008). Mcl-1 inhibition with S63845 attenuated airway inflammation by 73 % (p < 0.01) and reduced relapse rates from 67 % to 23 % (p < 0.01). Mcl-1 levels distinguished AA patients from healthy controls with 87 % sensitivity and 92 % specificity (AUC = 0.93, p < 0.001). In summary, targeting this axis provides a promising therapeutic strategy for refractory asthma.
Fruit allergy is a significant and increasingly recognized global health concern: once reported as a problem in Europe, it is now relevant in many countries, especially China, as consumption in both variety and quantity has increased dramatically. It is often associated with pollen allergy, with clinical manifestations ranging from localized oral allergy syndrome (OAS) to severe systemic reactions such as anaphylaxis. The majority of fruit allergens belong to a limited number of protein families each exhibiting distinct biochemical properties and clinical relevance. Allergy diagnosis relies on a detailed clinical history supported by in vivo and/or in vitro measurements. Component-resolved diagnosis (CRD) with purified allergen molecules provides insight into the primary sensitizing molecules and a more precise and standardized identification of sensitization patterns than possible with extract-based tests. Allergy management focuses on strict avoidance of trigger fruits, while prevention involves breeding hypoallergenic cultivars with lower allergen content and food processing technologies to reduce allergenicity. Allergen immunotherapy (AIT) has been explored as a treatment for fruit allergy with indications of improved tolerance. Emerging approaches combining AIT with biologic agents may further enhance treatment outcomes, although these novel strategies require additional research.
Background This study aimed to analyze literature published on the impact of lifestyle factors on allergies from 2015 to 2025. Methods This bibliometric analysis gathered data from the Web of Science Core Data Collection (WoSCC), using keywords such as “allergies”, “allergy”, and “lifestyle”. Further refinement included filtering for articles published between 2015 and 2025. Articles found through the WoSCC were generated using VOSviewer, and the generated maps were then analyzed. Results The maps focused on keywords, organizations, countries, and authors. 2,207 articles were analyzed, and The United States, England, and Germany published the most articles about lifestyle factors on allergies. In addition to this, keywords most involved “symptoms of allergies” and “test protocol”, as well as “sleep”, “exercise”, and “stress”. In a landscape of high-priced medicines and increasing inequality regarding social determinants of health, it is more important than ever to further understand how patients can change their lifestyles as a way of treating allergies and stay informed on what could affect their symptoms. Conclusion As time progresses, more studies and articles are written to achieve this goal, fueled by countries like the United States of America and by organizations like the University of Colorado, Icahn School of Medicine at Mount Sinai, and Northwestern University. This progress pushes the field of allergy and immunology closer to finding better solutions and treatments for allergy.
Allergic diseases have a high prevalence among populations worldwide affecting nearly 10-30% individuals. The gap between allergy incidence and currently available treatment options needs to be filled. Computational approaches aim to bridge this gap by utilizing and annotating existing knowledge on allergic proteins along with providing novel predictions and insights. In silico methods can be employed for identifying several factors pertaining to allergens such as structural characterization, determination of allergenicity of proteins, prediction of epitope sites, interactions with antibodies and immune receptors as well as in design of immune therapeutics. This review summarises the vital role of informatics in allergology and the exhaustive approaches available that assist in identification of novel aspects related to allergens.
Food allergies have surged in Western countries since the late 20th century. Despite the steady rate of food allergy prevalence since the 21st century, anaphylaxis incidence continues to rise. Recent studies indicated that food allergies and anaphylaxis are not uncommon in the developing world, but the trend in food allergy is marked by significant regional differences and urban-rural disparity. Globally, there is a discernible pattern of evolving allergen triggers associated with food protein-induced enterocolitis syndrome (FPIES), alongside the emergence of new food allergies, such as alpha-gal syndrome. Effective management of these allergies faces numerous challenges, including a lack of comprehensive data from developing nations. The global shortage of allergists, coupled with inconsistent access to care—particularly in low- to middle-income regions where epinephrine auto-injectors are often unavailable—further complicates the situation. Addressing these issues requires enhancing training for healthcare providers and establishing standardized practices to ensure comprehensive support for individuals with food allergies. The increasing instances of anaphylaxis underscore the need for strategies that extend beyond simple allergen avoidance. Recent innovations in food allergy treatment, including allergen immunotherapy (AIT) and alternative delivery methods like oral, epicutaneous, and sublingual immunotherapy, show great promise in desensitizing patients, particularly young children. Nonetheless, there remains a pressing need for more long-term safety studies and inclusive clinical trials. This article aims to examine the evolving landscape of food allergies globally and highlight critical gaps in our understanding and management, inspiring a collective effort to improve.
Objective To implement individualized nutritional therapy for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome children with suspected cow's milk protein allergy and explore the clinical effects of nutritional intervention via artificial intelligence methods. Methods A child diagnosed with IPEX syndrome received personalized nutritional intervention: oral short peptide formula showed poor efficacy in treating inflammatory bowel disease (IBD). Considering the possibility of secondary cow's milk protein allergy, the formula was adjusted to an extensively hydrolyzed formula on Day 31st day; blood glucose was controlled using the carbohydrate counting method. The efficacy of nutritional intervention was double-verified by the Bayesian Online Change Point Detection (BOCD) algorithm and the piecewise linear regression model. The analysis method centered on the McNemar test combined with the Generalized Estimating Equation (GEE) model was used to detect the efficacy of blood glucose control. Results After nutritional intervention, the blood glucose compliance rate was higher than that before the intervention. A significant inflection point in gastrointestinal symptoms appeared between days 32 to 35, the nutritional status was improved, and the therapeutic effect was verified. Conclusions Clinical nutritionist improve gastrointestinal symptoms and nutritional status in children with IPEX syndrome through personalized nutrition plans, promote disease stability, and lay the foundation for subsequent hematopoietic stem cell transplantation. When biological sample verification is unavailable, artificial intelligence (AI) provides certain guidance for diagnosis and efficacy assessment.
In allergic diseases, patients experience the recurrent suffering driven not only by adaptive immunity but also by non-adaptive immune memory, primarily mediated through epigenetic reprogramming. This review explores the role of inflammatory memory in common allergic conditions—such as asthma, rhinitis, food allergies, and atopic dermatitis—and synthesizes current research on its contribution to disease recurrence. Furthermore, we examine how different therapeutic strategies may alter disease progression by targeting inflammatory memory. Moving forward, advanced technologies like single-cell and spatial omics will be essential to unravel the complex landscape of inflammatory memory and develop precise, long-term treatments, ultimately enabling better management of allergic diseases.
