Journal of Investigational Allergology and Clinical Immunology最新文献

Background: Respiratory microbiome studies have improved our understanding of the various phenotypes and endotypes in heterogeneous asthma. However, the relationship between the respiratory microbiome and clinical phenotypes in children with asthma remains unclear. We aimed to identify microbiome-driven clusters reflecting the clinical features of asthma and their dominant microbiotas in children with asthma.

Methods: Induced sputum was collected from children with asthma, and microbiome profiles were generated via sequencing of the V3-V4 region of the 16S rRNA gene. Cluster analysis was performed using the partitioning around medoid clustering method. The dominant microbiota in each cluster was determined using linear discriminant effect size analysis. Each cluster was analyzed to identify associations between the dominant microbiota, clinical phenotype, and inflammatory cytokines.

Results: We evaluated 83 children diagnosed with asthma. Among 4 clusters reflecting the clinical characteristics of asthma, cluster 1, dominated by the genera Haemophilus and Neisseria, demonstrated lower postbronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) than the other clusters and more mixed granulocytic asthma. Neisseria correlated negatively with pre-BD and post-BD FEV1/FVC. Haemophilus and Neisseria correlated positively with programmed death-ligand (PD-L) 1.

Conclusions: To our knowledge, this study is the first to analyze the relationship between an unbiased microbiome-driven cluster and clinical phenotype in children with asthma. The cluster dominated by Haemophilus and Neisseria was characterized by fixed airflow obstruction and mixed granulocytic asthma, which correlated with PD-L1 levels. Thus, unbiased microbiome-driven clustering can help identify new asthma phenotypes related to endotypes in childhood asthma.

Introduction: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile evidence on the impact of medical, surgical, and biological treatment on olfactory outcomes in patients with CRSwNP.

Methods: This review was conducted by 2 reviewers according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence of all the studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP).

Results: Forty-four studies were included in the qualitative synthesis. These assessed sinonasal surgery (n=23), biologics (n=15), and conventional medical treatment (n=6). The methodological quality was moderate-to-high in most. Overall, significant improvements in the sense of smell were detected with all the interventions analyzed and measured using an objective tool, a subjective tool, or both. However, most studies used different outcome measures, thus hindering comparisons between interventions, and data on clinically relevant changes were missing.

Conclusion: Oral corticosteroids, biologics, and sinonasal surgery improve the olfactory impairment associated with CRSwNP. However, the heterogeneous nature of existing studies does not allow accurate comparisons.

Background and objective: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping.

Methods: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens.

Results: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes.

Conclusion: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Background: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, noninfectious complications are a major challenge among CVID patients.

Methods: All CVID patients registered in the national database were included in this retrospective cohort study. Patients were divided into 2 groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, noninfectious organ involvement, autoimmunity, and lymphoproliferative diseases were evaluated.

Results: Among 387 enrolled patients, 66.4% were diagnosed with noninfectious complications and 33.6% with isolated infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly more frequent among patients with B-cell lymphopenia. As for organ involvement, the dermatologic, endocrine, and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher than that of other types of autoimmunity not associated with B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were the most common type of malignancy. The mortality rate was 24.5%, and respiratory failure and malignancies were the most common causes of death, with no significant differences between the 2 groups.

Conclusions: Considering that some of the noninfectious complications might be associated with B-cell lymphopenia, regular patient monitoring and follow-up with proper medication (in addition to immunoglobulin replacement therapy) are highly recommended to prevent sequelae and increase patient quality of life.