Effects of mycophenolate mofetil on donor-specific antibody formation in renal transplantation

Clin Transplant. 2005 Apr;19(2):168-74. doi: 10.1111/j.1399-0012.2005.00261.x.

Abstract

Background: Mycophenolate mofetil (MMF) is a routinely used immunosuppressive agent that selectively blocks T- and B-lymphocyte proliferation. The present study was designed to investigate the effects of this drug on human leukocyte(HLA) antibody production in general and donor-specific antibody (DSA) formation in particular in 154 recipients of renal allografts.

Patients and methods: Renal allograft recipients were subdivided into three groups. Group 1 patients (n = 60) had received MMF since transplantation in combination with either cyclosporin A or tacrolimus and steroids. Group 2 patients (n = 29) had received an MMF-free immunosuppressive regimen initially followed by addition of MMF some time later. Group 3 patients (n = 65) had received no MMF. Cyclosporin A or tacrolimus in combination with azathioprine and/or steroids were used for immunosuppression. DSA were demonstrated by enzyme-linked immunosorbent assay (ELISA) for detection of panel-reactive antibodies of HLA class I and II specificity.

Results: The HLA antibodies were found in 16.7%, 27.6% and 30.8% of transplant recipients in groups 1, 2 and 3, respectively. DSA were found in 8.3%, 17.2% and 20.0%, and non-DSA in 10.0%, 20.7% and 24.6%, of patients in groups 1, 2 and 3, respectively.

Conclusion: The MMF reduces anti-HLA class I and II antibody production and consequently DSA production in renal allograft recipients. Our data indicate this effect to be more pronounced in patients given MMF immediately after transplantation than in those in whom MMF is introduced some time later. The presence of DSA in the serum of renal allograft recipients is associated with poorer graft function (higher serum creatinine and more rejection episodes).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation / drug effects*
  • Azathioprine / therapeutic use
  • Blood Transfusion
  • Cyclosporine / therapeutic use
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / physiology
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / immunology
  • Mycophenolic Acid / therapeutic use*
  • Reoperation
  • Steroids / therapeutic use
  • Tacrolimus / therapeutic use

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunosuppressive Agents
  • Steroids
  • Cyclosporine
  • IMP Dehydrogenase
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus