(208) - Novel Two-Hit Hypothesis for the Development of De Novo Autoimmunity Following Lung Transplantation

Abstract

De novo donor-specific HLA alloantibodies precede development of autoantibodies to lung-specific self-antigens following human lung transplantation and both strongly predispose to lung allograft rejection (LAR). The immunological link between allo- and auto- antibodies (Abs) remains unknown. Respiratory viral infections (RVI) are known risk factors of LAR and can lead to apoptosis of local CD4+CD25+foxp3+ regulatory T cells (Tregs). We hypothesize that anti-MHC Abs cause initial injury leading to the exposure of sequestered lung-specific antigens.