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Evaluating the Potential of Galactosaminogalactan as a Diagnostic Target for Invasive Aspergillosis

Summary

Researchers developed a new test to detect Aspergillus fungal infections using an antibody that recognizes a fungal component called GAG. The test worked very well in mouse studies, reliably detecting the fungus in blood and other body fluids. However, when tested with samples from infected patients, the test could not find GAG in the blood or other fluids, though it could see the fungus in lung tissue. This suggests either patients don’t produce enough GAG in their bloodstream, or something in human biology interferes with detection.

Background

Invasive aspergillosis (IA) is an opportunistic infection affecting immunosuppressed individuals with high mortality. Current galactomannan (GM) detection assays have limited sensitivity and specificity. Galactosaminogalactan (GAG), a secreted polysaccharide component of Aspergillus cell walls, presents a potential alternative diagnostic target.

Objective

To evaluate GAG as a diagnostic marker for invasive aspergillosis by generating a monoclonal antibody against GAG, developing a GAG ELISA, assessing cross-reactivity with other pathogens, and comparing GAG detection performance with GM detection in mouse models and human clinical samples.

Results

The GAG ELISA showed strong reactivity with Aspergillus fumigatus and A. flavus with no cross-reactivity to non-Aspergillus pathogens. GAG was successfully detected in mouse serum, BALF, and urine with strong correlation to fungal burden. However, GAG was undetectable in human serum, BALF, and urine samples despite being present in infected lung tissues.

Conclusion

While GAG ELISA demonstrates specificity and utility in mouse models of IA, failure to detect GAG in human samples suggests either insufficient circulating levels, epitope masking by host factors, or interference by naturally occurring GAG-specific antibodies in humans. Further investigation is needed to elucidate these discrepancies and determine GAG’s clinical diagnostic potential.
  • Published in:Mycoses,
  • Study Type:Experimental/Translational Research Study,
  • Source: PMID: 41060078, DOI: 10.1111/myc.70125
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