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

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.