SPECTRUM OF HUMORAL REJECTION AFTER PEDIATRIC HEART-TRANSPLANTATION

The deposition of immunoglobulin and complement 3 in the coronary microvasculature (humoral rejection) has been associated with poor outcome after heart transplantation. The purpose of this study is to relate the incidence of immunoglobulin and complement 3 myocardial deposition to the clinical course of pediatric heart transplant patients. One hundred thirty-one biopsy specimens from 30 patients, whose mean age at transplantation was 4.9 years (range, 2 days to 17 years), were processed for light microscopy and immunofluorescence. The mean follow-up was 25 months (range, 6 to 63 months). All patients underwent annual selective coronary artery angiography. No cellular or humoral rejection was seen in 97 biopsy specimens. Humoral rejection without cellular infiltrate was found in eight biopsy specimens from four patients (13%). Of 19 grade 1A, B (mild) biopsy specimens, 17 showed only cellular rejection, and two showed a mixed pattern of cellular and humoral rejection. Of six grade 2,3 (moderate) biopsy specimens, four showed only cellular rejection, and two showed a mixed pattern. The only grade 4 (severe) biopsy specimen revealed a mixed pattern. Three patients have had persistent immunoglobulin M and complement 3 deposits. One of these had angiographic evidence of accelerated graft coronary artery disease 2 years after transplantation, which was later confirmed at autopsy. Coronary artery disease has not been detected by serial angiography at 1 year (28 patients), 2 years (18 patients), 3 years (15 patients), 4 years (five patients), and 5 years (one patient). Humorally mediated rejection occurs with and without cellular rejection after pediatric heart transplantation. Humoral rejection may persist after treatment and resolution of severe cellular rejection episodes. Long-term immunofluorescence studies and coronary angiography will further define the relationship of persistent humoral rejection to graft coronary artery disease.