Background: As the use of multiplex specific IgE (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. The objective of this study was to assess the clinical and technical performance of the ALEX platform (MacroArray Diagnostics), in comparison to the ImmunoCAP ISAC 112 microarray and the ImmunoCAP singleplex method (ThermoFisher Scientific) in the diagnosis of pollen (cypress, grass, olive), dust mite Dermatophagoides pteronyssinus, Alternaria alternata, fruit (apple, peach) and nut (walnut, hazelnut and peanut) allergy. Methods: We enrolled 153 allergic patients and 16 non-atopic controls. sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and inter-assay, inter-batch and inter-lab reproducibility. Results: When measured globally (detection by one or more allergen components), ALEX2 showed adequate sensitivity and specificity for most of the allergens studied, comparable in general to that of ISAC112 (except for olive pollen and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis showed comparable results for all techniques, except for Ole e 1 and Jug r 3 in both ISAC112 and ImmunoCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. Conclusions: ALEX2 shows sound technical performance, and adequate diagnostic capacity, comparable in general to that of ISAC112 and ImmunoCAP for some aeroallergens and plant-food allergies in Mediterranean patients.

Background: Chronic histaminergic angioedema (CHA) is defined as recurrent episodes of isolated angioedema (without hives) of unknown cause that respond to the same treatment as chronic spontaneous urticaria (CSU). Quality of life (QoL) studies have not been performed for CHA, except those carried out in the context of CSU associated with angioedema attacks (CSU-AE). Moreover, biomarkers for monitoring disease activity in CHA have not been identified. We aim to describe the burden of CHA and impact on patient QoL, compare the findings to those in CSU-AE patients, and investigate biomarker associations with disease severity and QoL parameters. Methods: We performed a prospective multicenter study that included 68 patients with CHA and 63 patients with CSU-AE. Demographic and clinical variables were collected. Validated patient-reported questionnaires were employed to analyze the quality of life and disease activity. Blood and serological parameters, including blood cell count, C-reactive protein, D-dimer and total IgE, were also analyzed. Results: Angioedema disease activity was significantly higher in CSU-AE patients (median AAS7, IQR: 1, [0–1]) than CHA patients (0, [0–1]; p= 0.022). A considerable impact on QoL was found in both groups, although significantly worse values were found for CSU-AE (median AEQoL, IQR: 37, [10–65]; p=0.005). CHA patients were older than CSU-AE patients, and female predominance was not observed. Conclusions: Angioedema severity and QoL impacts are significantly worse in CSU than in chronic histaminergic angioedema. Angioedema should be included in severity urticaria scores (UAS) as well as in specific quality of life urticaria scales.