INTRAVENOUS IMMUNOGLOBULIN SUPPRESSION OF HLA ALLOANTIBODY IN HIGHLY SENSITIZED TRANSPLANT CANDIDATES AND TRANSPLANTATION WITH A HISTOINCOMPATIBLE ORGAN

Patients awaiting solid organ transplantation who are highly sensitize d to HLA antigens remain problematic in terms of finding compatible (c rossmatch-negative) donors. We have used intravenous gammaglobulin (IV IG; 10% Gamimune N) to determine both its efficacy in reducing panel-r eactive antibodies in vitro and the prognostic value of the in vitro t esting for in vivo efficacy. In 18 patients with PRAs ranging from 40 to 100% (mean: 77%) we found a reduction in absolute PRA of 4-70% (mea n decrease: 35%; percent inhibition: 4-100%; residual PRA 0-96%). In 7 cases, the residual antibody specificity could be easily determined a nd often appeared to include a short HLA-A2. This was independent of A 2 subtype as determined by PCR-SSOP Testing the MG on a panel of 21 HL A reagent alloantisera resulted in heterogeneous inhibitory patterns ( 7 complete, 3 partial, 8 differential, 3 none) independent of titer or specificity. In vivo administration to a 13-year-old kidney patient a waiting retransplant resulted in a PRA drop from 95% to 15% and succes sful retransplantation (now 11 months posttransplant). More impressive ly, successive in vivo administration of MG to a sensitized (anti-HLA- A2, A68, A69; B57, B58) heart transplant candidate resulted in success ful transplantation with an A2(+) histoincompatible heart. The patient experienced only one subclinical humoral rejection in the first 5 mon ths posttransplant. Biochemical studies to determine the effective com ponent of MG show that it is the IgG fraction and not soluble antigen or the minor IgM or IgA contaminants that is responsible. This suggest s an antiidiotypic modulation of anti-HLA antibodies in vitro and in v ivo.