What is Alpha-1 Antitrypsin (AAT)?
The Alpha-1 Antitrypsin (AAT) Test is a blood test that measures the level of alpha-1 antitrypsin, a protective protein produced by the liver.
This protein acts as a natural defense mechanism, particularly in the lungs. It helps neutralize enzymes such as neutrophil elastase, which are released during inflammation. While these enzymes are important for fighting infections, they can damage healthy lung tissue if not properly controlled.
Clinically, the AAT test is most often used to:
- Identify Alpha-1 Antitrypsin Deficiency (AATD), a genetic condition linked to lung and liver disease
- Investigate unexplained liver abnormalities, especially in infants, children, or young adults
- Evaluate early or unusual lung disease, particularly in people without significant smoking history
Where is Alpha-1 Antitrypsin Produced in the Body?
Alpha-1 antitrypsin is produced primarily in the liver and then released into the bloodstream. From there, it circulates to the lungs and other tissues, where it performs its protective role.
In individuals with certain genetic variants, the liver produces an abnormal form of AAT. This altered protein may accumulate within liver cells instead of being released efficiently into the blood. As a result, blood levels may be reduced—affecting lung protection—while the liver itself may be placed under stress.
Main Functions and Importance of Alpha-1 Antitrypsin
1. Protects the Lungs
AAT helps regulate the activity of enzymes released by white blood cells during inflammation. By limiting excessive enzyme action, it reduces unintended damage to lung tissue.
2. Supports Lung Structure
Adequate AAT levels help maintain normal lung elasticity and structure. When levels are reduced, lung tissue becomes more vulnerable during routine inflammatory processes.
3. Liver Protection
Normal production and release of AAT help prevent abnormal protein accumulation in liver cells, supporting long-term liver health.
4. Modulates Inflammation
AAT plays a broader role in controlling inflammatory responses throughout the body, contributing to tissue protection during infection or injury.
Causes of Low AAT Levels
Low AAT levels are most commonly linked to inherited Alpha-1 Antitrypsin Deficiency, caused by variations in the SERPINA1 gene. This condition follows an autosomal co-dominant inheritance pattern.
Other situations associated with reduced AAT levels include:
- Reduced liver production due to liver disease
- General protein loss states, such as nephrotic syndrome
- Severe nutritional deficiency affecting protein synthesis
Symptoms of Low AAT Levels
Low AAT levels themselves do not cause symptoms. Any clinical features are related to lung or liver involvement.
Lung-related features may include:
- Gradually increasing breathlessness
- Chronic cough or wheezing
- Recurrent respiratory infections
- Early development of airflow limitation
Liver-related features may include:
- Jaundice or abnormal liver blood tests
- Fatigue
- Abdominal swelling or organ enlargement
In infants and children, low AAT may be associated with prolonged jaundice or liver inflammation identified during early life.
Causes of High AAT Levels
Elevated AAT levels are usually reactive rather than genetic. AAT behaves as an acute phase reactant, meaning its levels rise temporarily during inflammation or stress.
Situations commonly associated with higher AAT levels include:
- Acute or chronic infections
- Inflammatory or autoimmune conditions
- Pregnancy
- Certain cancers
- Physical stress or tissue injury
Symptoms of High AAT Levels
High AAT levels do not cause symptoms on their own. Instead, they reflect the presence of an underlying inflammatory or disease process. In such cases, clinicians focus on identifying and evaluating the primary condition rather than the enzyme level itself.
Reference Ranges
Reference ranges may vary slightly between laboratories, but commonly accepted values include:
- Adults: 90 – 200 mg/dL
- Mildly reduced: 80 – 90 mg/dL
- Markedly reduced: below 80 mg/dL
Lower values raise suspicion for Alpha-1 Antitrypsin Deficiency and typically prompt further evaluation.
Sample Type and Handling
- Sample Type: Serum
- Collection Tube: Plain red-top or serum separator tube (SST)
- Fasting: Not required
- Special Note: Testing during active infection or inflammation may influence results
How the AAT Test is Performed
A blood sample is drawn from a vein, usually from the arm. The serum is separated and analyzed using standardized laboratory techniques that measure AAT concentration.
When hereditary deficiency is suspected, additional studies such as phenotyping or genotyping may be performed to better define the underlying genetic pattern.
Interpreting AAT Test Results
- Normal AAT: Adequate circulating protective protein
- Low AAT: Suggests inherited deficiency or reduced production/loss
- High AAT: Indicates inflammatory or stress-related response
Laboratory results are always interpreted alongside clinical findings and other investigations.
Test Preparation
No special preparation is needed.
Because AAT levels can rise during inflammation, testing is ideally performed when acute infections are not present, unless clinically indicated. Patients should inform their doctor about any known family history of lung or liver disease.
When to Consult a Doctor
Medical evaluation is recommended if you experience:
- Persistent breathlessness, wheezing, or chronic cough
- Signs of liver involvement such as jaundice or abdominal swelling
- Unexplained fatigue
- A family history of early-onset lung disease or liver problems
In such cases, the AAT test helps guide further diagnostic evaluation.
Important Word Explanations
- Alpha-1 Antitrypsin (AAT): A protein that protects tissues, especially the lungs, from enzyme-related damage
- Neutrophil Elastase: An enzyme released during inflammation that can harm lung tissue if uncontrolled
- AAT Deficiency: An inherited condition causing reduced AAT levels
- COPD: Chronic Obstructive Pulmonary Disease, affecting airflow and breathing
- Serum: The liquid portion of blood used for laboratory testing
- Acute Phase Reactant: A protein whose level increases during inflammation or stress
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