Serial study of circulating immune complexes before and after renal transplantation

To clarify the relationship of circulating immune complexes (CIC) to acute rejection or intercurrent infection, we studied the presence of CIC's by four methods in renal allograft recipients, by serial monitoring, before and after transplantation, of both CIC and donor-specific immunologic parameters. Three of the methods were dependent on the precipitation of CIC with low concentrations of polyethylene glycol (PEG). They were the radioisotopic conglutinin-binding assay, the Clq-binding assay, and the radial immunodiffusion (RID) of IgG and IgM in PEG precipitates. The fourth method was the Raji cell assay. These techniques were applied to sequentially collected serum samples from 26 patients, both before and up to 20 months after transplantation (mean followup, 7.2 months). CIC's were present in 14 out of 26 (54%) patients studied before transplantation. Glomerulonephritis was the primary renal disease in only half of these patients. Of this half, 12 (86%) were positive after transplantation, whereas only 2 of the 12 (17%) with no CIC before transplantation became positive subsequently. CIC's were demonstrable in 19 out of 28 patients (68%) during the posttransplant observation. In five instances (4 patients), they appeared only transiently (in 1 in association with rejection and in another 2 with intercurrent infection). In 14 patients, CIC's were detectable until the end of the observation period. In 23 rejection episodes in 16 renal allograft recipients, CIC's were present in association with 9 (39%) of these episodes, but the appearance or reappearance of CIC's coincided with rejection in only 5 of these episodes (or 22%). Thus, a cause-and-effect relationship is not established. In contrast, test for donor-specific immunologic monitoring, especially lymphocyte-mediated cytoxicity (LMC-D), became positive for 63% of the rejections and became negative when rejection activity subsided. CIC's were present at the time of only 4 of 15 infective episodes (27%). The fate of the allograft was no different in the CIC-positive group compared with those in whom they could not be detected. Among another 33 patients with long-surviving grafts (mean, 3.7 years) and studied for brief periods, CIC's were detected in 6 (18%). All 6 had excellent graft function though 1 had developed membranous glomerulonephritis.