Anti-inflammatory clinical-grade, plasma-derived human alpha-1 antitrypsin (hAAT) protects islets from allorejection as well as from autoimmune destruction. hAAT also interferes with disease progression in experimental autoimmune mouse models. hAAT increases T-regulatory (Treg) cell population size in animal models. Clinical-grade hAAT contains plasma impurities, multiple hAAT forms and various states of inactive hAAT. The authors thus wished to establish islet-protective activities and effect on Treg cells of plasmid derived circulating hAAT in whole animals. The authors conclude that plasmid-derived circulating hAAT protects islet allografts from acute rejection, and human plasma impurities are unrelated to islet protection. Future studies may use this in vivo approach to examine the structure-function characteristics of the protective activities of AAT by manipulation of the hAAT plasmid.
Shahaf, G., et al. (2011). Alpha-1-Antitrypsin Gene Delivery Reduces Inflammation, Increases T-Regulatory Cell Population Size and Prevents Islet Allograft Rejection. Mol Med. 17(9-10):1000-11.
Ramifications for Individuals with Type 1 Diabetes:
This study further establishes the use of hAAT as a safe and effective agent to protect islet transplant without the use of chronic immunosuppression.
This work was supported in part by JDRF through a Career Development Award to Dr. Lewis.