Clinical and Experimental Allergy最新文献

The last decades have shown the number of subjects developing allergic rhinitis (AR), allergic asthma (AA), atopic dermatitis (AD), and food allergy rose continuously worldwide. To cure these allergic diseases, allergen-specific immunotherapy (AIT) represents the unique treatment capable of providing clinical outcomes through the induction of long-term immunological tolerance. Despite proven efficacy, the duration of treatment, AIT-associated side effects, and the difficulty in identifying potential responders by diagnosis lead to poor patient compliance. Clinical investigations evidenced the role of blocking IgG antibodies induced by AIT in long-term tolerance. These observations suggested that passive allergy immunotherapy (PAIT) with low doses of allergen-specific blocking IgG antibodies represents an elegant alternative to frequent administrations of allergen extracts. Tremendous technological progress in the discovery/production of fully human monoclonal antibodies (mAbs) with very low immunogenicity has been made in the last decades, and these therapeutic antibodies revolutionised the treatment of cancers or infectious diseases. The recent advances in the isolation of rare allergen-specific IgE+ B cells and the generation of human antibodies in transgenic mice made possible the production of human monoclonal blocking antibodies against any allergen, sharing the same affinity with the corresponding naturally occurring IgE. This comprehensive review will describe the first promising preclinical and clinical data obtained with antibody cocktails targeting several IgE epitopes to some key single allergens. PAIT is safe and effective for the downregulation of the allergic response. Compared with conventional extract-based AIT, the positive outcomes could require much less dosing.

Background: Cannabis allergy is increasingly reported, with Can s 3 as a major allergen. Investigations into sensitisation to Can s 3 utilise sophisticated techniques, including the cytometric bead assay and the basophil activation test. This study aims to utilise a fluorescence enzyme immunoassay to quantify sIgE to Can s 3, employing a recombinant Can s 3 protein.

Methods: This study included 104 cannabis allergic patients, 20 healthy controls and 70 exposed atopic controls. Specific IgE by a fluorescence enzyme immunoassay or cytometric bead assay and the basophil activation test all used the same recombinant allergen. Two-graph ROC curves were used to determine the clinically validated allergen-specific cut-off for maximal sensitivity and specificity and to facilitate direct comparison of the test performances.

Results: Twenty-two individuals were non-responding in the basophil activation test and were excluded from all analyses involving basophil activation test results. The clinically validated cut-off points are > 0.16 kU_A/L, ≥ 0.14 kU_A/L and > 5% for a fluorescence enzyme immunoassay, cytometric bead assay and basophil activation test, respectively. Utilising these thresholds, the fluorescence enzyme immunoassay exhibited a sensitivity of 72% and specificity of 74%, the cytometric bead assay demonstrated a sensitivity of 49% and specificity of 89%. In responders, the basophil activation test exhibited a sensitivity of 51% and specificity of 82%. Remarkably, low positive fluorescence enzyme immunoassay results, particularly below 0.35 kU_A/L, are negative for both cytometric bead assay and basophil activation test. Conversely, utilising the conventional threshold of > 0.35 kU_A/L, the sIgE a fluorescence enzyme immunoassay results exhibited greater congruence with those of the cytometric bead assay and basophil activation test.

Conclusion: This study underscores the complexity of establishing an optimal decision threshold for the sIgE rCan s 3 fluorescence enzyme immunoassay and indicates that the clinically validated decision cut-off may not always represent the most efficacious approach.

Background: Prospective real-world data concerning the early and sustained effects of benralizumab on asthma control in patients with severe eosinophilic asthma (SEA) is lacking.

Methods: XALOC-2 is a prospective, observational, multi-national, real-world study in adults with SEA treated with benralizumab. This integrated analysis assessed Asthma Control Questionnaire (ACQ) scores, achievement of 3-component clinical remission (which included well-controlled symptoms [ACQ score ≤ 0.75], no exacerbations, and no use of maintenance oral corticosteroids [mOCS]), and other clinical outcomes, over a 12-month baseline period and up to Week 56. Associations between remission status and key baseline characteristics were also assessed.

Results: 535 patients were included. Median (interquartile range) ACQ score at baseline was 3.0 (2.2-3.8). At Week 1, 58.0% (282/486) of patients had ACQ score reductions of ≥ 0.5 points (minimal clinically important difference [MCID]) and 35.0% (170/486) had reductions of ≥ 1 point (2× MCID). By Week 56, these increased to 78.6% (276/351) and 62.1% (218/351), respectively. Improved asthma control after benralizumab initiation was similar irrespective of previous biologic use status. By Week 56, clinical remission criteria were achieved in 26.7% (70/262) of patients versus 0% (0/374) at baseline. No mOCS use, lower body mass index, better asthma symptom control and higher peak blood eosinophil count at baseline were associated with meeting 3-component clinical remission criteria at Week 56.

Conclusions: Real-world patients receiving benralizumab showed early and sustained improvements in asthma symptoms, regardless of previous biologic use. More than a quarter of patients achieved clinical asthma remission after 1 year of benralizumab treatment.