High sensitization to Rhizopus nigricans in children with allergic asthma in Southwest China: A microfluidic chip and proteomics study.

Abstract

Background: Fungi play a significant role in promoting acute exacerbations and poor control of allergic asthma (AA), particularly in children. In Southwest China, characterized by a humid and warm climate, moderate year-round fungal pollution is closely associated with the onset of childhood asthma. Despite this, little is known about the characteristics of fungal allergens in asthmatic children in this region.

Objective: This study aimed to investigate fungal sensitization in children with AA and its association with AA features.

Methods: A cross-sectional study was conducted at a children's hospital in Southwest China, involving 281 AA children and 20 healthy controls. Specific IgE (sIgE) levels for 13 fungal species and 3 Staphylococcal enterotoxins (SEs) were measured using microfluidic chips. Olink proteomics was used to analyze plasma samples from 46 AA children to explore molecular features associated with fungal sensitization.

Results: The sensitization rate to fungi and SEs in AA children was 75.4% (compared to 30% in healthy controls), with Rhizopus nigricans (RN) showing the highest sensitization rate at 67.3% (0% in healthy children). RN-sIgE was significantly correlated with total IgE (Rho = 0.76), D. pteronyssinus-sIgE (Rho = 0.67), D. farinae-sIgE (Rho = 0.67), blood eosinophil count (BEC, Rho = 0.26), fractional exhaled nitric oxide (FeNO, Rho = 0.20), and Childhood Asthma Control Test (C-ACT, Rho = -0.17). Proteomic analysis identified 61 upregulated plasma proteins in AA children with RN sensitization, including IL5RA, PRG2, PRSS2 and PRG3, forming a protein-protein interaction (PPI) network linked to innate immunity (53.1%) and proteolysis (21.9%). These proteins showed greater overlap with mycosis-associated proteins in the UK Biobank than with AA-associated proteins. A total IgE threshold of 395.0 kU/L statistically predicted RN sensitization with high accuracy (AUC 0.91) in this population. This was demonstrated in a case of refractory "nonallergic" asthma (negative for 19 common allergens) with an elevated total IgE level (461.4 IU/mL) and RN sensitization (0.72 IU/mL).

Conclusion: RN sensitization is relatively common in children with AA from Southwest China and may be associated with innate immune responses and proteolysis pathways. These findings suggest a possible underappreciation of RN's role in AA, warranting further investigation.