Serial Ten‐Year Follow‐Up of HLA and MICA Antibody Production Prior to Kidney Graft Failure

The role of HLA antibodies in chronic allograft rejection was examined utilizing a unique resource of sera collected annually and stored over a 12‐year period from patients with rejected or retained grafts. In patients selected for not having preformed HLA antibodies, 679 postoperative serial serum samples from 39 patients who rejected their grafts and 26 with functioning grafts were tested for HLA Class I and Class II antibodies by flow cytometry and for MICA antibodies by cytotoxicity on recombinant cell lines. HLA antibodies were found in 72% of patients who rejected grafts, compared to 46% with functioning transplants (p < 0.05). In addition, the incidence of IgG HLA plus MICA antibodies was higher (77%) among those with failed transplants than those with functioning transplants (42%) (p < 0.01). Finally, if patients with IgM anti‐HLA antibodies were included, 95% of the 39 patients who rejected their grafts had HLA or MICA antibodies, compared to 58% with functioning grafts (p < 0.01). Patients who rejected transplants had HLA and MICA antibodies more frequently than those with functioning grafts. These antibodies found in the peripheral circulation, were not necessarily donor‐specific, but their association with failure is consistent with a causality hypothesis.

[1]  P. Terasaki,et al.  Non-HLA lymphocyte cytotoxins in various diseases. , 2008, Tissue antigens.

[2]  K. Salmela,et al.  Weak Humoral Posttransplant Alloresponse after a Well–HLA-Matched Cadaveric Kidney Transplantation , 2004, Transplantation.

[3]  P. Terasaki,et al.  Predicting Kidney Graft Failure by HLA Antibodies: a Prospective Trial , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  E. Justrabo,et al.  Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy1 , 2003, Transplantation.

[5]  Susan Martin,et al.  The detection and definition of IgM alloantibodies in the presence of IgM autoantibodies using flowPRA beads. , 2003, Human immunology.

[6]  P. Dyer,et al.  Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome1 , 2003, Transplantation.

[7]  G. Zlabinger,et al.  Flow cytometry based detection of HLA alloantibody mediated classical complement activation. , 2003, Journal of immunological methods.

[8]  P. Terasaki,et al.  Almost all patients who are waiting for a regraft of a kidney transplant have anti-HLA antibodies. , 2002, Transplantation proceedings.

[9]  S. Takemoto,et al.  All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies , 2002, Transplantation.

[10]  J. Holgersson,et al.  Identification of the nonclassical HLA molecules, mica, as targets for humoral immunity associated with irreversible rejection of kidney allografts1 , 2002, Transplantation.

[11]  D. Mann,et al.  MIC expression in renal and pancreatic allografts. , 2002, Transplantation.

[12]  P. Stastny,et al.  Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients. , 2000, Human immunology.

[13]  D. Glotz,et al.  Antibodies to vascular endothelial cells in chronic rejection of renal allografts. , 2000, Transplantation proceedings.

[14]  P. Brenchley,et al.  An association between antibodies specific for endothelial cells and renal transplant failure. , 1998, Transplant immunology.

[15]  M. Yacoub,et al.  Anti-cell surface endothelial antibodies in sera from cardiac and kidney transplant recipients: association with chronic rejection. , 1997, Transplant immunology.

[16]  D. Geraghty,et al.  A second lineage of mammalian major histocompatibility complex class I genes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Tisone,et al.  Antidonor-HLA antibodies and soluble HLA antigens after kidney transplant. , 1993, Transplantation proceedings.

[18]  V. D’Agati,et al.  Soluble HLA antigens, anti-HLA antibodies, and antiidiotypic antibodies in the circulation of renal transplant recipients. , 1991, Transplantation.

[19]  T. Starzl,et al.  Posttransplant serum analysis in human kidney allografts. , 1981, Transplantation proceedings.

[20]  P. Terasaki,et al.  Cytotoxins in disease. Autocytotoxins in lupus. , 1970, The New England journal of medicine.

[21]  B. Lavingia,et al.  MICA is a target for complement-dependent cytotoxicity with mouse monoclonal antibodies and human alloantibodies. , 2002, Human immunology.

[22]  C. Ricordi,et al.  Kidney transplantation at the University of Miami. , 1999, Clinical transplants.