A Reevaluation of the Role of IgM Non-HLA Antibodies in Cardiac Transplantation

Abstract

Preexisting IgG antibodies to donor human leukocyte antigens (HLA) are a risk factor for rapid allograft rejection. However, non-HLA antibodies, of the IgM class, also called autoreactive antibodies, are not believed to affect graft survival. The aim of this study was to determine the incidence and clinical relevance of pretransplant lymphocytotoxic non-HLA IgM antibodies on long-term cardiac allograft survival. A retrospective study of 616 adult recipients of cardiac allografts, transplanted at this center between 1991 and 2003, has been performed. Antibodies in pretransplant sera were initially defined using complement-dependent cytotoxicity assays, and subsequently analyzed for HLA specificities using solid phase assays. HLA antibodies were present in 69 of 616 heart recipients (58 IgG, 11 IgM); in 22 of these, the antibodies were donor-specific. Non-HLA IgM antibodies were detected in 59 of 616 recipients who did not have HLA-specific antibodies; these patients had a 1, 2, 5, and 10 year survival of 55.9%, 54.2%, 49.9%, and 43.3% compared with 75.8%, 73.7%, 66.6%, and 52.8% for those without antibodies (P=0.0085 log-rank test). Multivariate analysis demonstrated pretransplant non-HLA IgM antibodies to be an independent risk factor for mortality (P=0.0001). Myocardial histology of postmortem heart and cardiac biopsies suggested an association with ischemic damage and "primary" allograft failure. We propose the hypothesis that the presence of cytotoxic IgM antibodies to non-HLAs before heart transplantation maybe a risk factor for early allograft failure.