Allergy最新文献

Background: The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self-proteins has been extensively studied, IgE responses induced by human-homologous exogenous molecular allergens (HEMAs) remains less understood.

Aim: To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.

Methods: We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer-ALEX-2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an 'IgE molecular-mimicry index' (IgE-MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE-MMI and AD, its severity, and response to dupilumab.

Results: IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non-HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE-MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3-11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4-37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9-15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7-302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02-0.8) and NPC-2 from dust mites (OR: 0.1, 95% CI: 0.01-0.9).

Conclusion: IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE-MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab.

As the world still vividly recalls the previous monkeypox (mpox) outbreak that impacted over 120 countries worldwide with more than 99,000 cases in 2022, we are now facing a second wave of infections from the monkeypox virus (MPXV), characterized by an exponential increase in cases. The current 2024 outbreak has already recorded more than 20,000 cases in Africa, marking a dramatic escalation compared to previous outbreaks. The predominance of the newly identified clade Ib variant, first detected in the Democratic Republic of the Congo (DRC) and now identified across multiple African nations and beyond, underscores its enhanced transmissibility and potential for international spread, evidenced by cases in Sweden and Thailand. The World Health Organization (WHO) declared on August 14, 2024, the current mpox outbreak a Public Health Emergency of International Concern (PHEIC), calling for heightened global public health measures. The ongoing pattern of unusual, frequent, and extensive outbreaks of mpox with potential global implications poses significant questions. This review addresses, in the format of 50 questions and answers, the 2024 mpox outbreak, detailing its characteristics, epidemiological data, and impact compared to previous outbreaks. It comprehensively explores critical questions related to MPXV virological characteristics, immunological response, clinical manifestations, epidemiology, diagnostics, and available treatments. The review also documents the significant and evolving challenges posed by the current mpox outbreak, highlighting its scale, spread, and public health response.

Background: Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group.

Methods: Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS).

Results: SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions.

Conclusion: This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

Background: Alteration of airway neuronal function and density and bidirectional interaction between immune cells and sensory peripheral nerves have been proposed to trigger and perpetuate inflammation that contribute to asthma severity. To date, few studies analysed neuroplasticity and neuroinflammation in tissue of asthmatic individuals. We hypothesized that the presence of these phenomena would be a pathological feature in fatal asthma.

Methods: We have quantified the expression of the pan-neuronal marker PGP9.5 and the neuronal sensory-derived neuropeptide calcitonin gene-related peptide (CGRP) in the large airways of 12 individuals deceased due to an asthma attack and compared to 10 control lung samples. The proximity between nerve bundles to eosinophils, mast cells and CADM1⁺ cells was also quantified. We have additionally developed a hPSC-derived sensory neuron/mast cell co-culture model, from where mast cells were purified and differences in gene expression profile assessed.

Results: Fatal asthma patients presented a higher PGP9.5 and CGRP positive area in the airways, indicating sensory neuroplasticity. Eosinophils, mast cells and CADM1⁺ cells were observed in close contact or touching the airway nerve bundles, and this was found to be statistically higher in fatal asthma samples. In vitro co-culture model showed that human mast cells adhere to sensory neurons and develop a distinct gene expression profile characterized by upregulated expression of genes related to heterophilic adhesion, activation and differentiation markers, such as CADM4, PTGS2, C-KIT, GATA2, HDC, CPA3, ATXN1 and VCAM1.

Conclusions: Our results support a significant role for neuroplasticity and neuroimmune interactions in fatal asthma, that could be implicated in the severity of the fatal attack. Accordingly, the presence of physical neuron and mast cell interaction leads to differential gene expression profile in the later cell type.

Human skin is colonized with skin microbiota that includes commensal bacteria, fungi, arthropods, archaea and viruses. The composition of the microbiota varies at different anatomical locations according to changes in body temperature, pH, humidity/hydration or sebum content. A homeostatic skin microbiota is crucial to maintain epithelial barrier functions, to protect from invading pathogens and to interact with the immune system. Therefore, maintaining homeostasis holds promise to be an achievable goal for microbiome-directed treatment strategies as well as a prophylactic strategy to prevent the development of skin diseases, as dysbiosis or disruption of homeostatic skin microbiota is associated with skin inflammation. A healthy skin microbiome is likely modulated by genetic as well as environmental and lifestyle factors. In this review, we aim to provide a complete overview of the lifestyle and environmental factors that can contribute to maintaining the skin microbiome healthy. Awareness of these factors could be the basis for a prophylactic strategy to prevent the development of skin diseases or to be used as a therapeutic approach.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.