Characterization of donor-directed antibody class in the post-transplant period using flow cytometry in renal transplantation

Abstract

Over the past few years there has been increasing awareness of the importance of humoral mechanisms in the rejection of renal transplants. In this study we have monitored the development of antibodies directed against donor T and B lymphocytes using the sensitive flow cytometric technique. Forty-two cadaveric renal transplants were studied both before and for a maximum of 14 days after transplantation. Donor cells were separated from spleen on the day of transplantation and stored in liquid nitrogen until required. The dual colour flow cytometric assay was used to detect IgG or IgM directed against donor T or B lymphocytes. Using AB sera as controls, results were expressed as relative median fluorescence (RMF) and then correlated with the clinical performance of the grafts. Significant associations were found between the incidence of donor-directed antibodies and the development of clinical rejection. The magnitude of the rise in antibody levels was also related to graft performance. In patients showing severe graft rejection, high levels of antibodies of the IgG class developed before the clinical diagnosis of rejection was made. The routine use of this test allows the prediction of impending severe rejection to be made and may have important implications for immunosuppressive therapy.

HLA matching for kidney transplantation

“…Nevertheless, a significant proportion of these transplants fail-some because of nonimmunologic causes having to do with the quality of the kidney or recurrence of disease, others because of rejection resulting from allorecognition of donor incompatibilities. Potential incompatibilities may be due to different alleles of HLA-A, -B, and -DR loci, as discussed in the following section; differences in antigens at other HLA loci, such as HLA-C, -DQ and -DP; or other molecules not traditionally matched such as HLA class I heavy-chain molecules encoded by MICA [4,40,41].…”

The role of B cells and alloantibody in the host response to human organ allografts

“…Pre‐transplant PRAs and donor‐specific anti‐HLA antibodies are both associated with impaired outcomes (69). Transplant recipients who develop anti‐HLA antibodies post‐transplant experience more rejection episodes (19, 64, 68, 70–75). In some studies, the magnitude of the rise in antibody levels was related to the severity of graft rejection (19, 71).…”

Clinical relevance of pretransplant human leukocyte antigen donor-specific antibodies in renal patients waiting for a transplant: A risk factor

“…Numerous studies have indicated a 2-to 10-fold higher incidence of acute rejection in the presence of HLA antibodies [16,[17][18][19][20][21][22]. The CDC method is a functional test because it detects complement-fixing antibodies (immunoglobulin (Ig)-M, IgG1, and IgG3) and these antibodies have been regarded as detrimental to the graft [3].…”