What are the implications of elevated Alpha-1 Antitrypsin (A1AT) levels?

From the Guidelines

Elevated Alpha-1 Antitrypsin (A1AT) levels are typically a normal physiological response to inflammation or infection in the body, rather than a disease state requiring treatment. No specific medication or intervention is needed for elevated A1AT levels alone. A1AT is an acute phase reactant protein produced by the liver that increases during inflammatory conditions such as infections, trauma, surgery, or chronic inflammatory diseases. The elevation serves a protective function, as A1AT inhibits proteolytic enzymes (particularly neutrophil elastase) that could otherwise damage healthy tissues during an inflammatory response. If you have elevated A1AT levels, your healthcare provider will likely focus on identifying and treating the underlying cause of inflammation rather than treating the elevated A1AT itself. Common causes include infections, autoimmune disorders, certain cancers, pregnancy, or use of estrogen-containing medications. Follow-up testing may be recommended to monitor levels once the underlying condition is addressed. This is different from alpha-1 antitrypsin deficiency, which is a genetic disorder requiring specific management, as noted in the American Thoracic Society/European Respiratory Society statement 1. Recent guidelines, such as the 2017 Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease report, also support the use of augmentation therapy in patients with alpha-1 antitrypsin deficiency, but this is not relevant to elevated A1AT levels in the context of inflammation or infection 1. Key points to consider include:

• Elevated A1AT levels are a normal response to inflammation
• No treatment is needed for elevated A1AT levels alone
• Underlying causes of inflammation should be identified and treated
• Follow-up testing may be recommended to monitor A1AT levels
• Alpha-1 antitrypsin deficiency is a separate genetic disorder requiring specific management.

From the Research

Implications of Elevated Alpha-1 Antitrypsin (A1AT) Levels

• Elevated A1AT levels are not directly associated with adverse health effects, but rather A1AT deficiency is linked to various diseases, including chronic obstructive pulmonary disease (COPD) and liver disease 2, 3, 4, 5, 6
• The primary function of A1AT is to protect the lungs from proteolytic damage by neutrophil elastase, and its deficiency can lead to premature development of pulmonary emphysema 2, 5
• A1AT deficiency can also cause liver disease due to the accumulation of mutant proteins in the endoplasmic reticulum of hepatocytes, leading to chronic liver disease and hepatocellular carcinoma (HCC) 2, 4
• The diagnosis of A1AT deficiency can be established by measuring serum A1AT concentration or through genetic analysis 3, 4
• Treatment options for A1AT deficiency include substitution therapy with human A1AT, which can help prevent the decline of pulmonary function and reduce lung infections 3, 5

Disease Associations

• A1AT deficiency is associated with:
  • Chronic obstructive pulmonary disease (COPD) 2, 3, 5, 6
  • Emphysema 2, 3, 5
  • Liver disease, including chronic liver disease and hepatocellular carcinoma (HCC) 2, 4
  • Bronchiectasis 6
  • Panniculitis 6

Treatment and Management

• Treatment options for A1AT deficiency include:
  • Substitution therapy with human A1AT 3, 5
  • Alpha1-antitrypsin replacement therapy 5, 6
  • Gene therapy 6
  • Possible future therapies, such as those based on stem cells 6