Detecting anti-donor antibodies by flow cytometry in pediatric kidney transplantation – is it necessary?

Background: Immune response after allotransplantation depends on type of transplanted organ, mismatching degree, type of immunosuppression, as well as genetic predisposition of the recipient. Donor-specific antibodies resulting from pre-transplant immunization, as well as produced during response to donor antigens trigger cascade of many events leading to ultimate organ destruction. The purpose of this study was to verify whether we need to apply more sensitive than standard methods to detect antidonor antibodies before transplantation.
Material/Methods: Two hundred and thirteen paediatric patients were transplanted based on negative results of complement dependent cross-match (CDC). Three-color flow cytometric cross-match (FCXM) detecting IgG and IgM antibodies against T and B lymphocytes was performed on sera taken immediately prior to transplantation. Immunosuppression protocol was selected irrespective from results of FCXM. Biopsy-proven rejection rate, graft loss during first month after transplantation, serum creatinine level one and three months after transplantation, as well as median serum creatinine after longest observation period were used to evaluate renal function.
Results: Despite negative results of CDC, antibodies against donor lymphocytes detected by FCXM were found in 21.1% cases, with similar frequency against T and B lymphocytes. Lower relative number of patients with creatinine <1.5 mg/dl and more frequent biopsy-proven rejection were observed among patients with positive FCXM. Early graft loss occurred more frequently among patients with positive FCXM, IgM antibodies or anti-T lymphocyte IgG. Poor renal function one month after transplantation was observed more frequently among patients with antibodies against B lymphocytes or anti-donor lymphocyte IgMs, but no effect of positive FCXM on long-term kidney graft function was observed.
Conclusions: Positive FCXM is an important, although not unique, risk factor of rejection-induced graft loss early after transplantation. Significance of individual correlations can be reduced i.e. by individually tailored immunosuppression regimen.

Keywords: Kidney Transplantation