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The Interaction of the AAT Protein with Alpha‐1 Antitrypsin Deficiency and Other Respiratory Disorders

Alpha‐1 antitrypsin (AAT) deficiency is a codominant genetic disease. Ordinarily, the liver makes large amounts of the protein AAT and releases it into the blood in its normal M form. It was hypothesized that if there is a deficiency of the AAT protein in the human body, which is caused by the misfolding of the Z variant of the protein in the liver, then AAT deficiency disorder occurs, which contributes to a multitude of lung and liver diseases. This Z variant results from an encoded misfolded variant where the glutamic acid in position 342 of the protein is replaced by a lysine. Structurally, AAT is a proteinase inhibitor and binds to human leukocyte elastase, which prevents damage to the lower respiratory tract. AAT deficiency is not a disease itself, but is considered a predisposition for the development of a number of diseases, mainly pulmonary emphysema and other chronic respiratory disorders. Through literature review as well as conversing with an expert on AAT protein and deficiency, it was found that the insufficient release of AAT into the blood causes low blood levels and increased susceptibility to respiratory diseases, as the function of the AAT protein is to provide protection to the lungs against such diseases. In its ideal functionality, conditions such as emphysema, cirrhosis, and COVID‐19 are protected against, but with AAT deficiency, the individual is more susceptible to these conditions. Although AAT deficiency is inherited genetically, environmental factors can contribute to the early onset of the disorder. Some examples are the utilization of lung irritants, such as smoking or vaping, as well as irritants in the forms of particles found in coal mining and steel millwork. Avoiding these environmental factors as much as possible can allow for an individual to mitigate symptoms of AAT deficiency for a prolonged period of time. Currently, there is no permanent cure to this disease other than frequent infusions, but there are various treatments under research. Studies have been focused on the geographical reach of AAT, as well as newly discovered and efficient treatment options for AAT deficiency. Researchers have been additionally synthesizing information pertaining to the AAT protein being heavily correlated with COVID‐19, which can aid in the research of similar respiratory diseases.