Significant changes in the alloantibody after lung transplantation in the cyclosporine treated rat model

The diagnosis of acute rejection after organ transplantation is often complicated by other possibilities, such as infection. Despite many attempts to identify rejection episodes after transplantation, only the detection of the humoral anti-human leukocyte antigen antibody has been effective in measuring alloimmunization, especially detected with flow cytometry cross-match (FCXM). As an initial step towards gaining a better understanding of the correlation between humoral responses and graft rejection in an immunosuppressant recipient, we investigated responses of alloantibodies (allo-Abs) after lung transplantation (LTx) in a rat model treated with adequate or inadequate cyclosporine A (CsA) therapy.

Orthotopic LTx was performed using a major histocompatibility complex fully incompatible combination (Brown Norway to Lewis rat). CsA was given subcutaneously to recipients at an optimal or a sub-optimal dosage for 3 days after transplantation. A FCXM technique was used to determine the time-course of changes in titers of allo-Abs in serum. The allo-Ab deposition in the grafted lung was detected with an immunofluorescent staining method.

Circulating IgM allo-Ab levels were significantly elevated on day 4 in both groups when histological findings revealed early stage of acute rejection. IgM levels in the sub-optimal dosage group were maximal and significantly higher than those in the optimal dosage group on day 4, and levels then decreased after day 8. IgG allo-Ab levels increased significantly on day 8 and continued to increase throughout the observation period.

Our data suggest that the monitoring IgM allo-Abs might be effective for identifying acute rejection in recipients with inadequate immunosuppression therapy.