Th1, Th2 and Monokine Responses as Risk Factors of Renal Transplant Rejection
Chronic transplant rejection remains the main cause of late kidney graft loss. We showed previously that patients with pretransplant CD4 helper defects and low in-vitro IL-10 responses demonstrated an extremely low risk of acute rejection and a significantly better 1- and 3-year graft function whereas pretransplant Th1 responses were not predictive (Weimer R et al. 1996 and 1998). In liver transplant recipients, we found CD4 helper function and in-vitro IL-10 responses significantly decreased compared to CsA-treated patients (Zipperle et al. 1997). If the same effect will be demonstrated in renal transplant recipients, Tacrolimus (Tacr) treatment might result in enhanced graft survival compared to CsA, when CD4 helper function and in-vitro IL-10 responses of the individual patient are elevated. Other studies of our group suggest a beneficial role of enhanced T-suppressor activity and of an IL-6 independent B cell/monocyte defect in the maintenance of long-term stable graft function, whereas enhanced monokine secretion (TNF-a, GM-CSF, IL-6) was found in chronic rejection (Weimer et al. 1990, 1992, 1994, 1998).
In the current randomized prospective study we will analyze the impact of CsA versus Tacr and of MMF versus azathioprine on Th1, Th2 and monokine responses and their predictive value regarding occurrence of acute and chronic rejection. With a proposed follow-up of 5 years this study might enable a patient-tailored immunosuppressive therapy resulting in prolonged graft survival.
Renal Failure, Chronic
Procedure: Kidney transplantation
Drug: cyclosporine A
Drug: mycophenolate mofetil
|Study Design:||Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Longitudinal
|Official Title:||Role of Th1, Th2 and Monokine Responses as Risk Factors of Acute and Chronic Renal Transplant Rejection – Impact of Different Immunosuppressive Protocols|
|Study Start Date:||January 1998|
|Study Completion Date:||January 2006|
|Department of Internal Medicine, University of Giessen|
|Giessen, Germany, D-35392|
|Principal Investigator:||Rolf Weimer, Prof. Dr.||Department of Internal Medicine, University of Giessen, Germany|