Desensitized Renal Transplant Recipients Show Reduced Cellular Responses to In Vitro Challenge

Abstract

Intravenous immunoglobulin (IVIG) desensitization protocols permit transplantation of sensitized renal recipients against alloantibody incompatibility barriers. It appears that IVIG induces a sustained down-regulation of alloantibody that facilitates crossmatch compatibility. However, the consequence of desensitization upon cellular immunity has not been addressed. We compared in vitro proliferative responses and cytokine expression between desensitized transplant recipients (IVIG) and non-IVIG-treated patients (controls). Eleven patients who were crossmatch-incompatible with living donors underwent treatment with IVIG and plasmapheresis. Nine patients converted to negative crossmatches and were transplanted. With a mean follow-up time of 17.6 ± 6.7 months, graft survival is 100%. Peripheral mononuclear cells were collected 12.5 ± 9 months after transplantation and tested for proliferative response and cytokine elaboration following challenge with staphylococcal enterotoxin b (SEB) and donor-specific mixed lymphocyte reaction (dMLR). Proliferative reactions were 90% lower ( P < .05) among IVIG versus controls in response to SEB and dMLR challenge. Cytokine response to SEB challenge was equivalent ( P = NS) between IVIG and controls. In contrast, cytokine elaboration was 60% lower ( P < .05) for IVIG versus controls in response to dMLR. One year after renal transplantation, desensitized patients showed in vitro hyporesponsiveness to superantigen and donor-specific challenge. This suggests that IVIG promotes a down-regulation in cellular immunity that may facilitate good graft outcome.