Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients

Circulation. 1999 Nov 9;100(19 Suppl):II229-35. doi: 10.1161/01.cir.100.suppl_2.ii-229.


Background: Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity.

Methods and results: Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency.

Conclusions: These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.

MeSH terms

  • Graft Rejection / prevention & control
  • Heart Diseases / immunology
  • Heart Diseases / physiopathology
  • Heart Diseases / surgery*
  • Heart Transplantation*
  • Heart Ventricles / immunology*
  • Heart Ventricles / physiopathology*
  • Heart-Assist Devices*
  • Histocompatibility Testing
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage*
  • Isoantibodies / immunology
  • Time Factors
  • Transplantation Immunology
  • Transplantation, Homologous


  • Immunoglobulins, Intravenous
  • Isoantibodies