Serum Concentration of IL-5 Receptor (IL-5R) and Associations with Disease Severity in Patients with Chronic Spontaneous Urticaria (CSU) and Atopic Dermatitis (AD).

The immunological pathogenesis of atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) has not been fully elucidated yet. The aim of our research was to assess the serum concentration of interleukin-5 receptor (IL-5R) in relation to the disease activity and pruritus intensity in adult patients with AD and CSU. This pilot study included 45 participants (15 patients with AD, 15 patients with CSU, and 15 healthy controls). Blood samples were taken to examine the serum levels of IL-5R using the enzyme-linked immunosorbent assay (ELISA) test. The Scoring Atopic Dermatitis (SCORAD) index, the Urticaria Activity Score (UAS7), and the Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that the IL-5R concentration was significantly higher in patients with CSU than in patients with AD and in the controls (p = 0.038). There was a positive correlation between the IL-5R level and the SCORAD index in patients with AD (r = -0.9, p = 0.047), which was not found for the CSU activity by UAS7 and with the pruritus severity by VAS in both examined groups of patients. Our findings underscore higher serum levels of IL-5R among CSU and AD patients, which may highlight its functional role in the pathogenesis of these diseases. In contrast, IL-5R might not be fully useful in reflecting the severity of symptoms. Although our results are promising, this study should be conducted on a larger cohort of patients.

Ceruloplasmin and oxidative stress in severe eosinophilic asthma patients treated with Mepolizumab and Benralizumab.

INTRODUCTION: Severe eosinophilic asthma has been associated with Th2 airway inflammation and elevated proinflammatory cytokines and chemokines, such as IL-5. Precision therapies have recently been shown to improve asthma symptoms with a steroid-sparing effect. Two such therapies, Benralizumab and Mepolizumab, humanized IgG antibodies directed against the IL-5 receptor and IL-5, have been approved for severe eosinophilic asthma. METHODS: Here we used a differential proteomic approach to analyse serum from patients with severe eosinophilic asthma treated with Benralizumab and Mepolizumab in a search for differential molecular modifications responsible of their effects. Enrichment analysis of differential proteins was performed for the two treatments. RESULTS AND DISCUSSION: After one month of Benralizumab treatment we detected up-regulation of certain protein species of the antioxidant ceruloplasmin. To investigate oxidative stress, we performed redox proteomics which detected lower oxidative burst after one month of Benralizumab treatment than in the pre-treatment phase or after one month of Mepolizumab therapy.

Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels.

BACKGROUND: Anti-IL-5 might be a useful therapeutic agent for eosinophilic disorders, yet its immunologic consequences have not been well characterized. OBJECTIVE: We sought to characterize the hematologic and immunologic effects of anti-IL-5 in human subjects. METHODS: The effects of 3-month infusions of mepolizumab were assessed in 25 patients with a variety of eosinophilic syndromes. Samples with increased IL-5 levels after therapy were analyzed by using size exclusion filtration. Immunoreactive IL-5 fraction and plasma samples were subsequently precipitated with saturating concentrations of protein A/G. RESULTS: Twenty-three patients responded to anti-IL-5 therapy with a decrease in blood eosinophil counts and a reduced percentage of CCR3(+) cells by 20- and 13-fold, respectively (P < .0001). Responsiveness was not related to the levels of baseline plasma IL-5 or the presence of FIP1L1-PDGFRA fusion gene. Persistently decreased blood eosinophilia remained for 3 months after final infusion in 76% of subjects. Therapy was associated with a large increase in blood IL-5 levels, likely because of a circulating IL-5/mepolizumab complex precipitated with protein A/G, a significant increase in eosinophil IL-5 receptor alpha expression, and increased percentage of CD4(+) and CD8(+) cells producing intracellular IL-5 (P < .05). Additionally, anti-IL-5 therapy decreased eotaxin-stimulated eosinophil shape change ex vivo. CONCLUSIONS: Anti-IL-5 therapy induces a dramatic and sustained decrease in blood eosinophilia (including CCR3(+) cells), decreased eosinophil activation, and increased circulating levels of IL-5 in a variety of eosinophilic disorders. Increased levels of IL-5 receptor alpha and lymphocyte IL-5 production after anti-IL-5 therapy suggest an endogenous IL-5 autoregulatory pathway.