Interpretation of Elevated Alpha‑1 Antitrypsin (A1AT) Levels

Pathophysiology of Elevated A1AT

An elevated A1AT concentration reflects an acute‑phase response to systemic inflammation, infection, tissue injury, recent surgery, or pregnancy rather than indicating A1AT deficiency. 1, 2, 3
Recent surgical procedures or tissue injury stimulate hepatic production of A1AT, leading to measurable increases in serum levels. 1

Elevated A1AT can mask underlying genetic deficiency; during acute inflammatory episodes levels may rise to as high as 1.4 g/L (140 mg/dL), producing falsely normal or elevated results. 1
Protein‑based A1AT testing should be avoided during acute illness, recent surgery, or active inflammation because these states artificially elevate the measurement and can obscure a true deficiency. 1
When clinical suspicion for A1AT deficiency remains high despite normal or elevated A1AT levels, clinicians should proceed directly to SERPINA1 gene sequencing rather than relying on repeat protein assays. 1

The following features mandate SERPINA1 genetic testing irrespective of the measured A1AT concentration:
1

Individuals with the severe‑deficiency PI*ZZ genotype exhibit a blunted acute‑phase response, yet their A1AT levels can still increase enough during inflammation to appear falsely reassuring. 1

In patients with elevated A1AT, simultaneous measurement of C‑reactive protein (CRP) is advised to assess concurrent inflammation.
For high‑risk patients who have suggestive clinical features, SERPINA1 gene sequencing should be performed regardless of A1AT or CRP results. 1

Alpha-1 antitrypsin (A1AT) behaves as an acute phase protein, meaning its serum concentration rises during inflammatory conditions, according to the Canadian Thoracic Society guidelines 4, 5, 6
The Canadian Thoracic Society explicitly warns that "serum level of A1AT fluctuates over time, notably increasing during acute inflammation" 4, 5, 6
Active infections (bacterial, viral, or fungal) can cause elevated A1AT levels 4, 5
Acute exacerbations of chronic diseases can also lead to elevated A1AT levels 4

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 4, 5, 6
The Canadian Thoracic Society notes that "levels as high as 1.4 g/L may be reached in some patients with A1AT deficiency during episodes of acute inflammation" 4, 5

When testing for A1AT deficiency, avoid testing during acute illness 4, 5, 6
If initial A1AT levels are borderline or normal but clinical suspicion remains high, proceed directly to DNA sequencing of SERPINA1 rather than relying on repeat protein measurements 4, 5, 6
The American Thoracic Society emphasizes that A1AT is "an acute phase reactant" and its levels must be interpreted in clinical context 7, 8