Pre-transplant immunological profile and risk factor analysis of post-transplant lymphoproliferative disease development: The results of a nested matched case-control study

Development of post-transplant lymphoproliferative disease (PTLD) is a major complication of organ transplantation. While immune mechanisms seem to play a major role in the development of PTLD, how the immune system contributes to the process of PTLD development or its regression remains unknown. Between 1990-1994, 303 organ transplant recipients were enrolled into a prospective study designed to analyze risk factors for PTLD. Using a nested case-control design, 9 PTLD and 18 control patients were matched for age, EBV serological status at the time of transplantation, and, in most cases, for the type of transplanted organ. The immunologic profiles of both groups were compared prior to and following transplantation. Immune measures included absolute numbers of lymphocytes and of subsets of T, B and natural-killer (NK) cells as well as spontaneous NK-cell and in vitro generated LAK-cell activities. A consistent trend for higher levels at baseline as well as following transplantation for almost all immune parameters was observed in patients who developed PTLD. A high absolute count of activated NK cells (CD56 + DR +) at baseline was found to be a significant predictor of PTLD development. The immunologic profile of patients who developed PTLD was consistent with pre- as well as post-transplant chronic immunologic stimulation, and not immunosuppression. In the PTLD group, 3 patients had pre-transplant autoimmune hepatitis and one had primary biliary cirrhosis, which suggests that the underlying presence of certain autoimmune disorders in organ transplant recipients might predispose to PTLD development.