Alpha-1 Antitrypsin Therapy for Autoimmune Disorders

Autoimmune diseases are conditions caused by an over reactive immune system that attacks self-tissues and organs. Although the pathogenesis of autoimmune disease is complex and multi-factorial, inflammation is commonly involved. Therefore, anti-inflammatory therapies hold potential for the treatment of autoimmune diseases. However, long-term control of inflammation is challenging and most of the currently used drugs have side effects. Alpha-1 antitrypsin (AAT) is an anti-inflammatory protein with a well-known safety profile. The therapeutic potential of AAT has been tested in several autoimmune disease models. The first study using a recombinant adeno-associated viral (rAAV) vector showed that AAT gene transfer prevented the development of type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model. Subsequent studies showed that treatment with AAT protein prevented and reversed type 1 diabetes. The beneficial effects of AAT treatment have also been observed in other autoimmune disease models such as rheumatoid arthritis and systemic lupus erythematosus. This paper reviews the therapeutic application of AAT and discusses possible mechanisms of action in various autoimmune diseases.