Alpha 1 antitrypsin deficiency7/6/2023 ![]() The target(s) of RA-associated autoantibodies appear to be citrullinated proteins. Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic joint inflammation and destruction. Alpha-1-Antitrypsin for Rheumatoid Arthritis (RA) Future studies will likely examine whether AAT treatment can be used as an anti-rejection agent for other organ transplantations. Given the anti-inflammatory effects of AAT, it was evaluated in combination with islet transplantation in mouse models, and AAT treatment significantly prolonged islet allograft survival. Allogeneic transplantation of islet cells has been considered as a treatment for T1D, but rejection of transplanted cells has remained a challenge. Dose optimization studies are in progress.Ī fascinating spin-off of these studies came from testing AAT as an anti-rejection agent in islet cell transplantation studies. Based on these preclinical studies, preliminary human trials of AAT treatment have been conducted and demonstrated that AAT was safe and well-tolerated in patients with new onset T1D. Direct treatment with clinical grade AAT also prevented or reversed diabetes in NOD mice. Using the non-obese diabetic (NOD) mouse model, investigators tested AAT gene therapy and found 70% of treated NOD mice remained diabetes-free for 8 months. T cell-driven autoimmunity and inflammatory factors contribute to the disease, and impaired AAT activity in T1D patients has been observed. Insulin insufficiency characteristic of T1D is due to autoimmune destruction of insulin-producing pancreatic beta cells. ![]() Examples of this are Type 1 Diabetes, Rheumatoid Arthritis, and Systemic Lupus Erythematosus 2: Alpha-1-Antitrypsin for Type 1 Diabetes (T1D) Infusions of AAT provide protection against proteases in the lung, and advances in treatment protocols continue to be made.Īlthough most commonly associated with lung disease, AAT deficiency is also associated with autoimmune and inflammatory diseases for which AAT therapy has shown promising results. As a result, levels of circulating AAT are severely reduced and frequently lead to cases of pulmonary emphysema. This mutation causes ~70% of AAT to be degraded in the liver and ~15-20% to be misfolded 1. Numerous mutations of the SERPINA1 gene have been identified, and many of these result in AAT deficiency the most common mutation associated with AAT deficiency is a single base-pair substitution of lysine for glutamate at position 342. The primary function of AAT is to protect normal body tissue from damage by nonspecific neutrophil proteolytic enzymes, such as neutrophil elastase which can attack lung elastin and compromise bronchial and alveolar wall integrity. Alpha-1-Antitrypsin (AAT) is a serine proteinase inhibitor (SERPIN) that in humans is encoded for by the SERPINA1 gene and is synthesized primarily by hepatocytes.
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