Polyclonal antithymocyte serum: immune prophylaxis and rejection therapy in pediatric heart transplantation patients

Abstract

Antithymocyte serum (ATS), a polyclonal antibody preparation raised in rabbits, has been used as rescue therapy for severe rejection and induction of immune prophylaxis in our pediatric patients with heart transplants. To evaluate the customized pediatric ATS dosages, circulating plasma levels of unbound ATS were measured by an indirect flow cytometric analysis. ATS blood levels and their effects on in vitro lymphocyte function (mixed lymphocyte culture), peripheral blood lymphocyte subsets (immunophenotyping), and in vivo response, as measured by echocardiographic or biopsy data, were studied in three pediatric transplant patient groups. Detectable levels of circulating ATS were present 24 hours after infusion and correlated with the decrease in CD2+ peripheral blood lymphocytes. As expected, detectable ATS levels were measured only in the ATS treatment groups. Significant differences in lymphocyte subsets were seen between patients receiving ATS and those never receiving ATS (p < 0.01), with the non-ATS patients having normal lymphocyte subset percentages (CD2 = 60% +/- 29%). The mixed lymphocyte culture response was suppressed to a greater degree in the ATS therapy groups (86% vs 75%, p < 0.02), although these results were confounded by the use of high-dose steroids in all groups, which inhibit allogeneic responses. We conclude that effective immunologic monitoring of ATS therapy can be accomplished by peripheral blood lymphocyte subset determinations and ATS serum levels.