Alpha-1 antitrypsin (AAT) is recognized as a novel immunomodulatory agent in autoimmune diseases and transplantation, however, its impact on neuroinflammation and neurodegeneration remains unknown.
GWASs also revealed that polymorphic variants of genes encoding proteinase 3 (PR3), the predominant antigenic target of ANCA in GPA, and its main inhibitor, alpha-1 antitrypsin, are highly associated with GPA and, even more significantly, with PR3-ANCA positivity (regardless of the clinical diagnosis); this emphasizes the central pathogenic role of PR3 and humoral autoimmunity in PR3-ANCA positive vasculitis.
Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.
This study demonstrates that AAT gene therapy attenuates cell-mediated autoimmunity, alters the T cell receptor repertoire, and efficiently prevents type 1 diabetes in the NOD mouse model.