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Anti-vimentin antibodies in transplant and disease
Tigran Divanyan1, Ernesto Acosta1, Dhruv Patel1
1Albany Medical College, Albany, NY, United States.
Non-HLA antibodies are recognized as a potential source of antibody mediated rejection following transplantation. The epitopes which lead to production of these antibodies are a result of tissue disruption, specifically endothelium, secondary to inflammation and injury. Vimentin is a cytoskeletal protein involved in many aspects of cellular organization, signaling, and proliferation. Recently, antivimentin antibodies have been shown to be important not only for rheumatological autoimmune diseases, but also cardiac and renal transplant dysfunction. In cardiac transplant recipients, antivimentin antibodies are associated with coronary artery vasculopathy and chronic graft loss. In renal transplantation, antivimentin antibodies are detected prior to transplantation and are also correlated with chronic graft dysfunction. In renal transplant recipients, antivimentin antibodies seen prior to transplantation are thought to be secondary to chronic endothelial injury during hemodialysis and therefore more prevalent prior to renal transplant than cardiac transplantation. In this review, we will examine the generation and pathogenesis of antivimentin antibodies. Given that these antibodies appear to be associated with both post-cardiac and -renal transplant dysfunction, developing standard detection paradigms may be important for risk stratification prior to transplantation. Finally, understanding the pathogenesis of antivimentin antibodies may lead to the development potential therapies in order to improve long-term survival.
Non-HLA antibodies are recognized as a potential source of antibody mediated rejection following transplantation. The epitopes which lead to production of these antibodies are a result of tissue disruption, specifically endothelium, secondary to inflammation and injury. Vimentin is a cytoskeletal protein involved in many aspects of cellular organization, signaling, and proliferation. Recently, antivimentin antibodies have been shown to be important not only for rheumatological autoimmune diseases, but also cardiac and renal transplant dysfunction. In cardiac transplant recipients, antivimentin antibodies are associated with coronary artery vasculopathy and chronic graft loss. In renal transplantation, antivimentin antibodies are detected prior to transplantation and are also correlated with chronic graft dysfunction. In renal transplant recipients, antivimentin antibodies seen prior to transplantation are thought to be secondary to chronic endothelial injury during hemodialysis and therefore more prevalent prior to renal transplant than cardiac transplantation. In this review, we will examine the generation and pathogenesis of antivimentin antibodies. Given that these antibodies appear to be associated with both post-cardiac and -renal transplant dysfunction, developing standard detection paradigms may be important for risk stratification prior to transplantation. Finally, understanding the pathogenesis of antivimentin antibodies may lead to the development potential therapies in order to improve long-term survival.
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