What does a positive Aspergillus‑specific immunoglobulin M (IgM) result indicate, and how should it be interpreted and managed in immunocompromised patients (such as those with neutropenia, hematologic malignancy, solid‑organ transplantation, or prolonged corticosteroid use) and in patients with allergic bronchopulmonary aspergillosis (ABPA)?

Aspergillus-Specific IgM Testing

Clinical Utility and Interpretation

Aspergillus-specific IgM testing is not recommended for routine clinical use, as it has limited diagnostic value across all forms of aspergillosis and is not included in current diagnostic guidelines. 1

Evidence Against IgM Testing

• The European Respiratory Society guidelines explicitly state that measuring A. fumigatus IgM antibodies is not recommended (Strength of Recommendation D, Quality of Evidence III) due to insufficient data demonstrating clinical value. 1

• In chronic pulmonary aspergillosis (CPA), IgM showed poor sensitivity of only 43.9% with specificity of 87.2%, making it an unreliable diagnostic marker. 2

• IgM may have modest utility only in subacute invasive aspergillosis (SAIA), where the positive rate was 63%, but this drops precipitously to 46.7% in patients sick for 3-6 months and becomes 0% in patients with disease duration ≥6 months. 2

Recommended Antibody Testing Instead

For chronic pulmonary aspergillosis and ABPA, Aspergillus-specific IgG is the recommended antibody test, not IgM. 1

• All patients suspected of having chronic or subacute invasive aspergillosis should be tested for A. fumigatus IgG antibody or precipitins (Strength of Recommendation A, Quality of Evidence II). 1

• IgG has sensitivity of 84.1% and specificity of 89.6% for CPA diagnosis, substantially superior to IgM performance. 2

• The presence of anti-Aspergillus IgG antibodies differentiates between infected and colonized patients with a positive predictive value of 100% for detecting infection. 1

ABPA-Specific Considerations

In ABPA diagnosis, the focus is on IgE (both total and Aspergillus-specific) and IgG, not IgM. 1, 3

• The 2024 revised ISHAM-ABPA working group criteria require A. fumigatus-specific IgE ≥0.35 kUA·L⁻¹ and serum total IgE ≥500 IU·mL⁻¹ as essential components. 1

• Elevated A. fumigatus-specific IgG (≥27-40 mgA·L⁻¹ depending on population) serves as one of the "other components" supporting ABPA diagnosis alongside eosinophilia and imaging findings. 3

• IgM testing plays no role in the ABPA diagnostic algorithm. 1

Immunocompromised Patients

In immunocompromised patients with suspected invasive pulmonary aspergillosis, antibody testing (including IgM) has extremely limited utility. 1, 4

• These patients often cannot mount adequate antibody responses due to their immunosuppressed state, making serology unreliable. 1

• Diagnosis relies instead on galactomannan (GM) antigen detection in bronchoalveolar lavage fluid (sensitivity 77-86%, specificity 76-77%) or serum, Aspergillus-specific PCR, and culture. 1

• Even Aspergillus-specific IgG, which is useful in immunocompetent patients with CPA, has limited value in neutropenic or severely immunocompromised patients. 4

Key Clinical Pitfalls

• Do not order IgM testing when evaluating for any form of aspergillosis—it adds no diagnostic value and may cause confusion. 1

• If IgM is inadvertently ordered and returns positive, interpret with extreme caution as it has poor sensitivity and does not reliably indicate active infection. 2

• Focus diagnostic efforts on validated tests: IgG and IgE for CPA/ABPA in immunocompetent patients, and GM antigen/PCR/culture for invasive disease in immunocompromised patients. 1