Diseases Associated with Elevated Alpha-1 Antitrypsin Levels
Elevated serum alpha-1 antitrypsin (A1AT) levels occur primarily during acute inflammatory states, as A1AT is an acute phase reactant that increases in response to systemic inflammation, infection, malignancy, and tissue injury.
Understanding A1AT as an Acute Phase Protein
The critical distinction here is that A1AT behaves as an acute phase protein, meaning its serum concentration rises during inflammatory conditions 1. This physiological response can complicate diagnostic testing for A1AT deficiency, as the Canadian Thoracic Society guidelines explicitly warn that "serum level of A1AT fluctuates over time, notably increasing during acute inflammation" 1.
Clinical Conditions Associated with Elevated A1AT:
Acute inflammatory states:
- Active infections (bacterial, viral, or fungal) 1
- Acute exacerbations of chronic diseases 1
- Systemic inflammatory response syndrome 2
Chronic inflammatory conditions:
- Active rheumatoid arthritis 3
- Inflammatory bowel disease 2
- Chronic obstructive pulmonary disease with active inflammation 4
Malignancies:
Tissue injury and stress:
Critical Clinical Implications
The elevation of A1AT during inflammation creates a diagnostic pitfall: Patients with underlying A1AT deficiency may have falsely normal or even elevated A1AT levels during acute illness 1. The Canadian Thoracic Society specifically notes that "levels as high as 1.4 g/L may be reached in some patients with A1AT deficiency during episodes of acute inflammation" 1.
Prognostic Significance in COPD
Research demonstrates that chronically elevated A1AT levels in COPD patients (without genetic deficiency) correlate with worse outcomes 4. A 10-year prospective study found that COPD patients with higher serum A1AT levels (>141 mg/dL) showed:
- More rapid annual decline in FEV1 4
- Higher 10-year mortality 4
- Worse systemic inflammation status 4
- Higher blood neutrophil counts 4
This paradoxical finding suggests that persistently elevated A1AT reflects ongoing systemic inflammation rather than protective antiprotease activity 4.
Practical Testing Recommendations
When testing for A1AT deficiency, avoid testing during acute illness 1. If initial A1AT levels are borderline or normal but clinical suspicion remains high (early-onset COPD before age 40, minimal smoking history <10 pack-years, panlobular emphysema, family history), proceed directly to DNA sequencing of SERPINA1 rather than relying on repeat protein measurements 1.
The American Thoracic Society emphasizes that A1AT is "an acute phase reactant" and its levels must be interpreted in clinical context 1, 2.