Treatment with anti-MHC-class-II antibody postpones kidney allograft rejection in primates but increases the risk of CMV activation.
Treatment of kidney graft recipients with antibodies that may specifically suppress the anti-donor response would be an ideal situation to prevent graft rejection. MHC class-II-specific antibodies and, in particular, DR specific antibodies have often been proposed as treatment to prevent antigen presentation, and thus graft destruction. Here we report an attempt to prevent graft rejection using a humanized MHC class-II-specific monoclonal antibody CDP855 in a cynomolgus monkey kidney graft model. A modest delay in graft rejection was observed when the antibody was given only on days 0, 1 and 2 after transplantation. Unexpectedly 50% of the animals succumbed of a viral infection, most likely CMV in two of three cases, prior to graft rejection in the first week post-transplantation. We speculate that the antibody treatment triggered CMV activation, possibly as a consequence of the activation of factors such as NF-kappab by the interaction of the antibody and its target cells.
Jonker
Margreet
M
Biomedical Primate Research Centre, Rijswijk, The Netherlands. jonker@bprc.nl
Ringers
Jan
J
Kuhn
Eva-Maria
EM
't Hart
Bert
B
Foulkes
Roland
R
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000453:epidemiology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008252:Macaca fascicularis; D011183:Postoperative Complications / Q000453:epidemiology
D000906:Antibodies; D000949:Histocompatibility Antigens Class II