title: Role of anti-vimentin antibodies in allograft rejection.
abstract: Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.
authors.affiliation: National Heart and Lung Institute, Imperial College, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK. Electronic address: Marlene.rose@imperial.ac.uk.
authors.forename: Marlene L
authors.initials: ML
authors.lastname: Rose
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D051379:Mice; D023421:Models, Animal; D011183:Postoperative Complications / Q000276:immunology*; D011323:Primates; D014181:Transplantation Immunology; D014746:Vimentin / Q000276:immunology*
chemical_list: D000906:Antibodies; D014746:Vimentin
keywords: AMR; AVA; CFA; HMEC; MMF; PAF; anti-vimentin antibodies; antibody mediated rejection; complete Freund’s adjuvant; human microvascular endothelial cells; mycophenolate mofetil; platelet activating factor