The human body produces a protective protein called Serpin A1, more commonly known as alpha-1 antitrypsin (AAT). This protein originates in the liver, is released into the bloodstream, and travels throughout the body. Serpin A1 belongs to a larger family of proteins known as serpins and is encoded by the SERPINA1 gene.
The Function of Serpin A1 in the Body
The principal role of the Serpin A1 protein is to inhibit powerful enzymes called proteases. Its main target is neutrophil elastase, an enzyme that is part of the immune response. While this enzyme helps fight infection, its activity must be controlled to prevent it from breaking down the body’s own healthy tissues.
Serpin A1 acts as a guardian by neutralizing excess neutrophil elastase. This protective action is particularly important in the lungs, where delicate tissues are highly susceptible to destruction by this enzyme. By controlling elastase, Serpin A1 helps maintain the structural integrity and function of the lungs.
Understanding Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency (AATD) is a genetic condition caused by mutations in the SERPINA1 gene. This inherited disorder results in the body’s inability to produce sufficient quantities of functional AAT protein. The condition is passed from parents to children through an autosomal codominant inheritance pattern, meaning each parent contributes one copy of the SERPINA1 gene.
The severity of the deficiency depends on the specific gene variants, or alleles, a person inherits. The normal version of the gene is the ‘M’ allele, while the most common variants that cause a deficiency are the ‘S’ and ‘Z’ alleles. Individuals with two ‘M’ alleles (MM) have normal AAT levels, while those who inherit one deficiency allele (MS or MZ) may have reduced levels but often produce enough protein to remain healthy. A severe deficiency occurs in individuals who inherit two deficiency alleles, most commonly the ‘ZZ’ genotype.
Associated Health Conditions
The lack of sufficient AAT protein leads to different health problems, primarily affecting the lungs and the liver through distinct mechanisms. The risk and presentation of these conditions can vary among individuals, even those with the same genetic makeup. Environmental factors, especially cigarette smoking, play a large part in the progression of lung-related diseases.
Lung Disease
In the lungs, AATD allows neutrophil elastase to continuously attack and break down elastin, a protein that gives lung tissue its flexibility and strength. This destruction of the alveolar walls impairs the lungs’ ability to expand and contract, leading to early-onset emphysema and chronic obstructive pulmonary disease (COPD). Symptoms often include shortness of breath, chronic cough, and wheezing, which may first appear between the ages of 20 and 50. Tobacco smoking accelerates this process, causing more rapid and severe lung damage in individuals with AATD.
Liver Disease
The mechanism of liver damage in AATD is different from the lung disease. In individuals with certain gene variants, particularly the ‘ZZ’ genotype, the AAT protein produced is misfolded. Much of this abnormal protein gets stuck and accumulates inside liver cells, forming polymers. This buildup is toxic to the cells, causing damage and inflammation. Over time, this chronic injury can lead to scar tissue (fibrosis), cirrhosis, and an increased risk for liver cancer. This issue can manifest at any age, from causing jaundice in newborns to leading to chronic liver disease in adults.
Diagnosis and Treatment Approaches
Identifying AATD begins with a blood test that measures the concentration of AAT protein. If the level is low, genetic testing is used to identify the specific SERPINA1 gene variants, which confirms the diagnosis and helps predict the risk of associated health conditions.
Treatment for AATD is tailored to the specific organ affected. For individuals with lung disease, the primary treatment is augmentation therapy, which involves regular intravenous infusions of AAT protein from human plasma. This therapy raises the level of AAT in the blood and lungs, helping to slow the progression of tissue destruction. For liver disease, treatments focus on managing symptoms, and in cases of severe liver failure, a transplant may be the only effective option. Lifestyle changes, most importantly the complete avoidance of smoking, are a foundational part of managing the condition.