The relevance of a more sensitive crossmatch assay to renal transplantation.

While the importance of the standard preoperative crossmatch in predicting renal graft success is accepted, a more rapid and sensitive assay may be of additional clinical benefit. We have developed a flow cytometric assay to detect the presence of antibodies (IgG) in the recipient sera directed against donor lymphocytes, prior to transplantation. This assay is more rapid and sensitive than the conventional cytotoxic test. In a clinical study the sera of 75 renal graft recipients were tested, all of which were negative in their conventional crossmatch; 12 of these were identified as having T cell-directed IgG, and 4 had B cell antibody. Graft failure was not significantly different in the positive and negative antibody groups, as defined by flow cytometry (P = 0.147, chi square test). The incidence of postoperative complications was studied in the 60 grafts functioning at three months. Recipients with donor B or T cell directed antibodies had a longer primary nonfunction (P = 0.0098, Mann-Whitney U test), and showed a higher number of rejection episodes (P = 0.014, Mann-Whitney U test); accordingly they were more likely to require strong immunosuppressive agents such as OKT3 or ATG (P less than 0.05, chi square test). Patients with donor-directed antibodies were also hospitalised for a longer period (P = 0.015, Mann-Whitney U test) and had a higher creatinine level 3 months after transplantation (P = 0.021 Mann-Whitney U test). This study shows that the described preoperative flow cytometric crossmatch is capable of defining a population of renal transplants who form an at-risk group. Thus this assay has considerable potential in pretransplant matching of recipients with a particular graft donor.