title: Alloantibody-associated chronic rejection of MHC class I-disparate heart grafts is modulated by intravenous soluble donor alloantigen.
abstract: Increasing evidence suggests that there may be a causal relationship between the development of donor-specific alloantibodies and chronic allograft vasculopathy (CAV). PVG.RT1(u) rat heart allografts spontaneously undergo chronic rejection when transplanted into unmodified PVG.R8 congenic recipients that differ only at the classical MHC class I RT1.A locus. Here we show that development of vasculopathy in this experimental model is associated with production of a strong anti-A(u) antibody response. Perioperative intravenous administration of recombinant soluble RT1.A(u) heavy chain that is sequence identical to donor MHC class I, or chimaeric A(u/a) (donor/recipient) protein had a variable effect resulting generally in either sensitisation and accelerated rejection, or abrogation of alloantibody and attenuation of chronic rejection. These findings highlight the potential for soluble donor MHC class I alloantigen given at the time of heart transplantation to influence alloantibody production and graft outcome.
authors.affiliation: Department of Surgery, University of Cambridge School of Clinical Medicine, Box 202, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Easterfield
authors.forename: Luc
authors.initials: L
authors.lastname: Delriviere
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Wallduck
authors.forename: Sivasuriya
authors.initials: S
authors.lastname: Sivaganesh
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Bolton
mesh_terms: D000818:Animals; D004333:Drug Administration Routes; D005805:Genes, MHC Class I / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000379:methods; D007518:Isoantibodies / Q000276:immunology*; D007519:Isoantigens / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats
chemical_list: D007518:Isoantibodies; D007519:Isoantigens