Antithymocyte globulin is associated with complement deposition in cardiac transplant biopsies

Polyclonal antithymocyte globulin preparations contain antibodies with reactivity to endothelial cells. Therefore, we investigated whether treatment with this reagent caused complement deposition in human cardiac transplants. Frozen tissue was available from endomyocardial biopsies of 75 patients, who were transplanted between April 1995 and April 2000. Nine of these patients were converted from cyclosporin A (CsA) to horse antithymocyte globulin (ATGAM) in the first month after transplantation. All of the biopsies were stained by immunofluorescence for C4d as evidence of activation of the classical pathway of complement. In addition, biopsies from patients treated with ATGAM and control patients were stained for deposition of horse immunoglobulin (Ig)G. All nine patients who received ATGAM had deposition of horse IgG and C4d. Two color stains demonstrated that the horse IgG colocalized with the C4d staining. No staining for horse IgG or C4d was evident in biopsies obtained before ATGAM treatment. Likewise, no staining for horse IgG was detected in seven control patients who had C4d staining. Most patients treated with ATGAM had no histologic evidence of rejection, but did have myocyte damage and macrophage infiltration. Thus prophylactic treatment with ATGAM is associated with the deposition of horse IgG and activation of complement in the transplant.