title: The autoimmune response to vimentin after renal transplantation in nonhuman primates is immunosuppression dependent.
abstract: BACKGROUND
  Chronic allograft nephropathy (CAN) is a common late complication of kidney transplantation. Antibodies to both human leukocyte antigen and nonhuman leukocyte antigen antigens have been implicated in the development of this condition. Here we investigated the presence of antivimentin antibodies in nonhuman primate recipients of kidney allografts as a possible predictor of CAN and the effects of immunosuppression.
  
  
  METHODS
  Thirty seven rhesus monkeys received a kidney allograft to study the potency of several different immunosuppressive regimens (conventional immunosuppression, n=19, vs. costimulatory blockade, n=18). Monkeys were tested for antivimentin antibody by enzyme-linked immunosorbent assay and for anti-donor antibody by staining donor spleen cells with recipient serum. The appearance of antibodies was correlated with the graft pathology in biopsy and necropsy material.
  
  
  RESULTS
  Antivimentin antibodies were found in 31 of 37 animals, whereas only 15 of 32 animals made anti-donor antibodies. Conventional immunosuppression did not prevent antivimentin antibody formation. Costimulation blockade, in particular blocking CD40 and CD86, significantly delayed or prevented antivimentin antibody formation, but did not prevent CAN. Antivimentin antibodies were not significantly associated with development of CAN.
  
  
  CONCLUSIONS
  We postulate that vimentin acts as an autoantigen after renal transplantation; it elicits an autoimmune response that is not regulated by cyclosporine. This autoimmune response may be part of the complex immunologic events occurring posttransplantation and may contribute to the development of CAN, but cannot be considered as a major cause of CAN because this condition also develops without antivimentin antibodies.
authors.affiliation: Biomedical Primate Research Centre, Rijswijk, The Netherlands. jonker@bprc.nl
authors.forename: Margreet
authors.initials: M
authors.lastname: Jonker
authors.forename: Anna
authors.initials: A
authors.lastname: Danskine
authors.forename: Krista
authors.initials: K
authors.lastname: Haanstra
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wubben
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Kuhn
authors.forename: Marlene
authors.initials: M
authors.lastname: Rose
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D015703:Antigens, CD / Q000096:biosynthesis; D015551:Autoimmunity; D051940:B7-2 Antigen; D001706:Biopsy; D019013:CD40 Antigens / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000941:Antigens; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D014746:Vimentin