We have studied 56 human hearts before and after transplantation for the presence of immunoglobulin M. None of the 56 time-zero biopsy specimens studied contained immunocytochemically detectable immunoglobulin M, but they all had immunoglobulin M deposits on vascular endothelial cells after transplantation. The vascular location of immunoglobulin M was confirmed in double-antibody experiments with antibodies to von Willebrand factor and immunoglobulin M. None of the immunoglobulin M antibody reactivity was shown to colocalize with complement. Biopsy specimens from 29 of the 56 patients contained abundant deposits of immunoglobulin M. These patients were clinically stable, and only one of them has died. Biopsy specimens from 27 of the 56 patients had scant deposits of immunoglobulin M. These patients were clinically unstable; eight of them have died, and one has undergone retransplantation. In addition, biopsy specimens from stable allografts contained fewer fibrin deposits than biopsy specimens from unstable grafts, suggesting a protective role for non-complement fixing immunoglobulin M. The observation that immunoglobulin deposits were found soon after transplantation prompts us to consider them to be natural antibodies. Efforts to identify the antigen for immunoglobulin M natural antibodies in heart transplant recipients are currently under study.
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