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

Abstract

Patients awaiting solid organ transplantation who are highly sensitized to HLA antigens remain problematic in terms of finding compatible (crossmatch-negative) donors. We have used intravenous gammaglobulin (IVIG; 10% Gamimune N) to determine both its efficacy in reducing panel-reactive antibodies in vitro and the prognostic value of the in vitro testing 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% (mean decrease: 35%; percent inhibition: 4–100%; residual PRA 0–96%). In 7 cases, the residual antibody specificity could be easily determined and often appeared to include a short HLA-A2. This was independent of A2 subtype as determined by PCR-SSOP. Testing the IVIG on a panel of 21 HLA 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 awaiting retransplant resulted in a PRA drop from 95% to 15% and successful retransplantation (now 11 months post-transplant). More impressively, successive in vivo administration of IVIG to a sensitized (anti-HLA-A2, A68, A69; B57, B58) heart transplant candidate resulted in successful transplantation with an A2+ histoincompatible heart. The patient experienced only one subclinical humoral rejection in the first 5 months posttransplant. Biochemical studies to determine the effective component of IVIG show that it is the IgG fraction and