Serum IgG in Hypersensitivity Pneumonitis
Serum IgG testing against HP-associated antigens should be performed as supportive diagnostic evidence but cannot confirm or exclude the diagnosis of hypersensitivity pneumonitis on its own. 1
Diagnostic Performance
Test Characteristics Against Other ILDs
The most clinically relevant comparison shows serum IgG testing distinguishes HP from other interstitial lung diseases with sensitivity of 83% and specificity of only 68%—characteristics that the ATS/JRS/ALAT guideline committee unanimously deemed suboptimal. 1 This poor specificity means nearly one-third of patients with other ILDs will test falsely positive, making the test inadequate as a standalone diagnostic tool.
Test Characteristics Against Control Populations
- Unexposed controls: Sensitivity 93%, specificity 100% 1
- Exposed controls: Sensitivity 90%, specificity 91% 1
These excellent characteristics against control populations are misleading for clinical practice, as the real diagnostic challenge is distinguishing HP from other ILDs, not from healthy individuals.
Clinical Interpretation Pitfalls
Critical Caveat: Positive Test ≠ Causation
A positive serum IgG result only indicates prior exposure to an antigen at some point in the patient's life—it does not prove that exposure caused the lung disease. 1 This is the most important clinical pitfall to avoid. The test identifies potential exposures worthy of environmental investigation, not definitive diagnoses.
Negative Test ≠ Exclusion
Given the 83% sensitivity against other ILDs, approximately 17% of HP patients will have negative serum IgG testing. 1 The test cannot reliably exclude HP.
Exposure-Test Discordance
Studies demonstrate significant discordance between exposure history and serology:
- 60% of patients with positive precipitins reported no identifiable exposure 1
- 25-32% of patients with negative precipitins had identifiable exposures 1
This discordance further undermines the test's reliability as a standalone diagnostic tool.
Technical Considerations
Testing Method
ELISA performs best among available methods. 1 Both ELISA and precipitin testing show similar overall performance, though ELISA demonstrates slight superiority in distinguishing HP from other ILDs. 1
Antigen-Specific Performance
Test performance varies by HP subtype, with best results for:
- Metal worker's lung
- Farmer's lung
- Bird fancier's lung
- Bagassosis 1
The 2021 CHEST guideline noted sensitivity ranges from 25% to 96% and specificity from 60% to 100% depending on the antigen tested, serological method, and cutoff values used. 1 This extreme heterogeneity reflects lack of standardization across laboratories.
Guideline Recommendations
ATS/JRS/ALAT 2020 Position
The guideline suggests (not recommends) performing serum IgG testing for both nonfibrotic and fibrotic HP when the differential diagnosis includes HP, but with very low confidence in the estimated effects. 1 The voting was split, with substantial numbers voting against or abstaining, reflecting the controversy around this test.
CHEST 2021 Position
The CHEST guideline concluded there is insufficient evidence to support the utility of serum antigen-specific antibody testing to reliably confirm or rule out HP diagnosis. 1 They cited very low-quality evidence with multiple methodological concerns including incorporation bias, inappropriate reference standards, and lack of generalizability.
Role in Diagnostic Algorithm
Serum IgG testing functions as one component in a multifactorial diagnostic framework that includes:
- Detailed exposure history (most critical element) 2
- High-resolution CT findings 2
- BAL lymphocytosis (when performed) 1
- Histopathology (when obtained) 1
The diagnostic confidence level increases when serum IgG positivity is combined with compatible HRCT findings and/or BAL lymphocytosis, but never reaches "definite" confidence without histopathology. 1
Practical Clinical Approach
When serum IgG testing is positive:
- Use results to guide targeted environmental investigation in the patient's home, workplace, and social environments 1
- Do not interpret as diagnostic confirmation 1
- Proceed with additional diagnostic testing (HRCT, BAL, potentially biopsy) based on clinical context 2
When serum IgG testing is negative:
- Do not exclude HP from the differential diagnosis 1
- Continue comprehensive exposure assessment 2
- Consider that up to 60% of HP cases never have an identifiable antigen despite thorough investigation 2
Major Limitations
The lack of standardized testing methods, antigen panels, and cutoff values across laboratories severely limits the generalizability and reproducibility of serum IgG testing. 1 Many facilities lack access to locally relevant antigens and must rely on commercial panels that may not include region-specific exposures. 1