Does Cross-Reactivity Occur in the Fungal Antigen Assays?

Complete cross-reactivity occurs in the Histoplasma and Blastomyces galactomannan antigen assays in specimens from patients with histoplasmosis or blastomycosis (table). The antigen detected in these infections is identical. There is no need to order both. The two assays use different standard curves accounting for different concentrations, typically 2-4 ng higher in the Histoplasma assay than the Blastomyces assay. For example, the concentration may be 6.5 ng/mL in the Histoplasma assay and 4.2 ng/mL in the Blastomyces assay.

Lesser cross-reactivity occurs between these galactomannan antigens and Coccidioides antigen, which is a different class of galactomannan. In this case the antigen concentration helps distinguish a true-positive result from a cross reaction. For example, in coccidioidomycosis cases the Coccidioides antigen may be 4.2 ng/mL while the Histoplasma cross reaction is 0.4 ng/ml.

Even less cross-reactivity occurs between the galactomannan antigens detected in histoplasmosis, blastomycosis, or coccidioidomycosis and the Aspergillus galactomannan, and the true positive result is higher than the cross reaction.

No cross reaction occurs between the galactoxylomannan detected in cryptococcosis and the galactomannans detected in histoplasmosis and blastomycosis, but studies of crossreactivity in cryptococcosis and coccidioidomycosis have not been conducted. Weakly positive cross reactions (0.5-1.5 units) may occur in the Aspergillus galactomannan assay in serum from patients with cryptococcosis with concentrations of cryptococcal antigen >1: 512. High levels of Aspergillus galactomannan (>7units) in patients with aspergillosis do not cross react in the cryptococcal galactoxylomannan assay.

Cross-reactivity patterns have not been reported with non-Aspergillus molds and algae.

Mycosis Antigen Assay Cross-Reactivity
Histoplasmosis Blastomycosis Coccidioidomycosis Cryptococcosis Aspergillosis
Histoplasma NA Complete Moderate None Slight
Blastomyces Complete NA Moderate None Slight
Coccidioides Moderate Moderate NA Unknown Unknown
Cryptococcus None None Unknown NA Slight
Aspergillus Slight Slight Unknown None NA