SPECTRUM OF HUMORAL REJECTION AFTER PEDIATRIC HEART-TRANSPLANTATION

The deposition of immunoglobulin and complement 3 in the coronary micr ovasculature (humoral rejection) has been associated with poor outcome after heart transplantation. The purpose of this study is to relate t he incidence of immunoglobulin and complement 3 myocardial deposition to the clinical course of pediatric heart transplant patients. One hun dred thirty-one biopsy specimens from 30 patients, whose mean age at t ransplantation was 4.9 years (range, 2 days to 17 years), were process ed for light microscopy and immunofluorescence. The mean follow-up was 25 months (range, 6 to 63 months). All patients underwent annual sele ctive coronary artery angiography. No cellular or humoral rejection wa s seen in 97 biopsy specimens. Humoral rejection without cellular infi ltrate was found in eight biopsy specimens from four patients (13%). O f 19 grade 1A, B (mild) biopsy specimens, 17 showed only cellular reje ction, and two showed a mixed pattern of cellular and humoral rejectio n. Of six grade 2,3 (moderate) biopsy specimens, four showed only cell ular rejection, and two showed a mixed pattern. The only grade 4 (seve re) biopsy specimen revealed a mixed pattern. Three patients have had persistent immunoglobulin M and complement 3 deposits. One of these ha d angiographic evidence of accelerated graft coronary artery disease 2 years after transplantation, which was later confirmed at autopsy. Co ronary artery disease has not been detected by serial angiography at 1 year (28 patients), 2 years (18 patients), 3 years (15 patients), 4 y ears (five patients), and 5 years (one patient). Humorally mediated re jection occurs with and without cellular rejection after pediatric hea rt transplantation. Humoral rejection may persist after treatment and resolution of severe cellular rejection episodes. Long-term immunofluo rescence studies and coronary angiography will further define the rela tionship of persistent humoral rejection to graft coronary artery dise ase.