Role of Aspergillus IgG in Diagnosis and Management of ABPA
Elevated Aspergillus fumigatus-specific IgG is an important component for diagnosing ABPA, serving as one of the key criteria alongside A. fumigatus-specific IgE, but has limited utility in monitoring treatment response. 1
Diagnostic Value of Aspergillus IgG in ABPA
According to the 2024 revised ISHAM-ABPA working group consensus criteria, positive IgG against A. fumigatus is one of the "other components" (any two required) for diagnosing ABPA, alongside the essential components of A. fumigatus-specific IgE ≥0.35 kUA·L−1 and serum total IgE ≥500 IU·mL−1 1, 2
A. fumigatus-specific IgG can be detected using lateral flow assays or enzyme immunoassays, with population-specific cut-offs recommended (e.g., ≥27 mgA·L−1 for India, ≥60 mgA·L−1 for Japan, and ≥40 mgA·L−1 for the UK) 1
Research has shown that A. fumigatus-specific IgG has high sensitivity (88-89%) and specificity (100%) for diagnosing ABPA, making it significantly more sensitive than traditional Aspergillus precipitins testing (27.4% sensitivity) 3
Age-dependent cut-offs have been proposed: 60 mg/L for patients aged <55 years and 45 mg/L for those aged ≥55 years, due to an observed age-dependent decline in Af-IgG levels 4
Role in Diagnostic Algorithm
In the diagnostic algorithm for ABPA, elevated A. fumigatus-IgG or lateral flow assay (LFA) is considered alongside A. fumigatus-specific IgE ≥0.35 kUA·L−1, serum total IgE ≥500 IU·mL−1, and blood eosinophil count ≥500 cells·μL−1 1
When combined with A. fumigatus-specific IgE, IgG testing provides improved diagnostic accuracy for differentiating ABPA from severe asthma with fungal sensitization (SAFS), with one study showing 82.3% sensitivity and 78.6% specificity when using combined cutoffs of Af-IgG >1,000 U/mL and Af-IgE >1.00 kU/L 5
A. fumigatus-specific IgG can be elevated in other conditions including COPD, pulmonary tuberculosis, bronchiectasis, and chronic pulmonary aspergillosis, requiring careful clinical correlation 1
Limitations in Treatment Monitoring
Unlike total IgE, which typically declines by approximately 50% after successful treatment, A. fumigatus-specific IgG has shown inconsistent patterns during treatment response 3, 6
Research indicates that A. fumigatus-specific IgG may actually increase in 37.2% of patients following treatment, making it unreliable for monitoring treatment response 3
During ABPA exacerbations, A. fumigatus-specific IgG decreases in only about 23.1% of cases, compared to total IgE which increases by >50% in 92.3% of exacerbations 3, 6
Practical Considerations and Pitfalls
There is a high probability of misclassifying ABPA as allergic bronchopulmonary mycosis (ABPM) if IgE and IgG against Aspergillus species are performed using non-standardized assays 1
In settings where fungus-specific serology is not available, ABPM may be pragmatically diagnosed if there is repeated and consistent culture growth, serum total IgE ≥500 IU·mL−1, peripheral blood eosinophilia and radiological features of ABPM, provided the Aspergillus-specific serology is negative 1
The British Thoracic Society guideline notes that immunoprecipitation techniques to detect Aspergillus-specific IgG antibodies have been largely replaced by ELISA, which has higher sensitivity (41-46%) compared to counter immuno-electrophoresis (15%) 1
Delayed diagnosis of ABPA is common (average 10 years from symptom onset), highlighting the importance of appropriate serological testing including Aspergillus-specific IgG in at-risk populations 7