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Background: Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use. Objective: To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission. Methods: We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment. Results: A statistically significant reduction of FeNO50 values and J'awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 (p = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, p = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb). Conclusion: These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy. [ABSTRACT FROM AUTHOR]

The total and SARS-CoV-2-specific antibody content in convalescent plasma (CP) samples from Bulgarian donors and their therapeutic potential for COVID-19 patients was subjected to characterization. CPs (n = 90) were obtained after informed consent at National Centre of Transfusion Hematology in Sofia, Bulgaria, in the period 01 June 2021 and were tested for RBD-IgG, RBD-IgA and anti-nuclear antibodies (ANA) by semi-quantitative ELISA. Concentrations of total IgG, IgG isotypes, IgA, and IgM, as well as of 25 Th1, Th2, Th17 and regulatory cytokines were determined for all samples; concentrations of Neutralizing antibodies against six SARS-CoV-2 variants were determined in Receptor-Binding Domain (RBD-positive) samples (Luminex xMAP technology). Concordant production of RBD-specific IgG and IgA was detected in 45 (50%); 12 (13.3%) were RBD-IgG single-positive, 8 (8.8%) RBD-IgA single-positive, and 25 (27.7%) – double negative. Absence of neutralizing activity was documented for 8/65 (12.3%) of RBD-positive samples. No correlation existed between the levels of RBD-IgG and RBD-IgA and the total neutralizing activity of CPs (p > 0.05). Total IgG, IgA, IgM and IgG Isotype concentrations did not differ from reference values. Increased concentrations of IL-18, IL-27, IL-1Ra, IL-21 and IL-22 were detected in most tested samples (80% respectively). The comparison between 45 RBD-double positive and 25 RBD-double negative CPs showed significant differences for the concentrations of IL-22 (2.4 vs 40, p < 0.05) and IL-10 (1 vs 15, p < 0.001). All CPs were ANA negative. Detailed characterization for SARS-CoV-2 specific antibody content and cytokine concentrations might improve the results of CPs application for in early stage treatment in resource-limited settings. [ABSTRACT FROM AUTHOR]

The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments. [ABSTRACT FROM AUTHOR]

Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period. The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity. [ABSTRACT FROM AUTHOR]

Objective: Both patients and physicians may be hesitant toward vaccination in patients with asthma, which may result in lower vaccine uptake. The aim of this work was to investigate the vaccination rate, the adverse reactions, as well as the factors associated with vaccine acceptance and hesitancy toward COVID-19 vaccination among asthmatic patients in Beijing. Methods: A multi-center, cross-sectional face-to-face survey was conducted in patients with asthma consecutively recruited from December 2021 to April 2022. The survey included asthma status, COVID-19 vaccine uptake and adverse reactions, and knowledge of and attitude toward COVID-19 vaccination. Results: A total of 261 patients were enrolled. The rate of COVID-19 vaccination during the study period was 73.6%, as compared to 87.64% in the general population in China. Patients who were currently working, had received other vaccines in the past, and had had no adverse reactions to other vaccines, showed a higher rate of COVID-19 vaccination. Patients believing that the vaccination of family members and colleagues had a positive impact on their decision to get vaccinated, were more likely to get the COVID-19 vaccines. The COVID-19 vaccination rate was lower in those with poorly monitored asthma and those using biologic therapies. The adverse effects of COVID-19 vaccines in asthmatic patients were similar to those in the general population. Conclusion: The COVID-19 vaccination rate in asthmatic patients was lower than the general population in China. Active measures should be taken to control asthma and increase vaccination rates in these patients. [ABSTRACT FROM AUTHOR]

With a growing knowledge of Inborn errors immunity (IEI), immunological profiling and genetic predisposition to IEI phenocopies have been developed in recent years. Here we summarized the correlation between various pathogen invasions, autoantibody profiles, and corresponding clinical features in the context of patients with IEI phenocopies. It has been extensively evident that patients with anti-cytokine autoantibodies underly impaired anti-pathogen immune responses and lead to broad unregulated inflammation and tissue damage. Several hypotheses of anti-cytokine autoantibodies production are summarized here, including a defective negative selection of autoreactive T cells, abnormal germinal center formation, molecular mimicry, HLA class II allele region, lack of auto-reactive lymphocyte apoptosis, and other possible hypotheses. Phenocopies of IEI associated with anti-cytokine autoantibodies are increasingly recognized as one of the causes of acquired immunodeficiency and susceptibility to certain pathogen infections, especially facing the current challenge of the COVID-19 pandemic. By investigating clinical, genetic, and pathogenesis autoantibodies profiles associated with various pathogens' susceptibilities, we could better understand the IEI phenocopies with anti-cytokine autoantibodies, especially for those that underlie life-threatening SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb. [ABSTRACT FROM AUTHOR]

In humans, blood circulating IgM+IgD+CD27+ B cells are considered analogous to those described in the marginal zone of the spleen and are involved in important immunological processes. The homing receptors they express, and the organs involved in their development (for example, intestinal organs in rabbits) are only partially known. We recently reported that this population is heterogeneous and composed of at least two subsets: one expressing high levels of IgM – IgMhi B cells – and another low levels – IgMlo B cells. To evaluate the expression of homing receptors on IgD+CD27+ IgMhi and IgMlo B cells and quantify their frequencies in blood of control and appendectomized and/or tonsillectomized volunteers. Using spectral flow cytometry, the simultaneous expression of 12 previously reported markers that differentiate IgMhi B cells and IgMlo B cells and of α4β7, CCR9, CD22 and CCR10 were evaluated in blood circulating B cells of control and appendectomized and/or tonsillectomized volunteers. The existence of phenotypically defined IgMlo and IgMhi B cell subsets was confirmed. They differentially expressed intestinal homing receptors, and the expression of α4β7 and CCR9 seems to determine new IgM subpopulations. IgMlo and IgMhi B cells were detected at lower frequencies in the appendectomized and/or tonsillectomized volunteers relative to controls. Human blood circulating IgD+CD27+ IgMlo and IgMhi B cell subsets differentially express homing receptors, and it is necessary to investigate if mucosal organs are important in their development. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA), a severe inflammatory respiratory disease, is caused by a hypersensitivity reaction to the colonization of the airways with Aspergillus fumigatus. It is most often described in patients with asthma or cystic fibrosis. The diagnosis of ABPA is based on a combination of clinical, radiological, and immunological findings that have been included in different diagnostic criteria over the years. In this paper, we review the biomarkers included in these diagnostic criteria and novel research biomarkers that may be used in the diagnosis and treatment follow-up of ABPA in cystic fibrosis. [ABSTRACT FROM AUTHOR]

Local allergic rhinitis (LAR) is a clinical rhinitis phenotype characterized by the presence of nasal symptoms of AR in nonatopic patients with a negative skin prick test and undetectable specific IgE (sIgE) in serum against inhalant allergens but with a positive nasal allergen provocation test. This study evaluated the effectiveness of a 12-month course of sublingual immunotherapy (SLIT) for house dust mite (HDM) allergies in adult patients with confirmed LAR and concomitant asthma. The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12-month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed. Results: In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group. Conclusion: SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs. [ABSTRACT FROM AUTHOR]

As one of the most important weapons against infectious diseases, vaccines have saved countless lives since their first use in the late eighteenth century. Antibodies produced by effector B cells upon vaccination play a critical role in mediating protection. The past several decades of research have led to a revolution in our understanding of B cell response to vaccination. Vaccines against SARS-CoV-2 coronavirus were developed at an unprecedented speed to power our global fight against COVID-19 pandemic. Nevertheless, we still face many challenges in the development of vaccines against many other deadly viruses, such as human immunodeficiency virus (HIV) and influenza virus. In this review, we summarize the latest findings on B cell response to vaccination and pathogen infection. We also discuss the current challenges in the field and the potential strategies targeting B cell response to improve vaccine efficacy. Key abbreviations box: BCR: B cell receptor; bNAb: broadly neutralizing antibody; DC: dendritic cells; DZ: dark zone; EF response: extrafollicular response; FDC: follicular dendritic cell; GC: germinal center; HIV: human immunodeficiency virus; IC: immune complex; LLPC: long-lived plasma cell; LZ: light zone; MBC: memory B cell; SLPB: short-lived plasmablast; TFH: T follicular helper cells; TLR: Toll-like receptor [ABSTRACT FROM AUTHOR]