Innate immune functions in kidney transplantation

Abstract

The innate immune system plays an important role in solid organ transplantation. This thesis focuses on the role of the lectin pathway of complement activation in kidney and simultaneous pancreas-kidney transplantation (SPKT) and describes the role of properdin in tubular complement activation and clearance of apoptotic cells. Mannose-binding lectin (MBL) is the initiating molecule of the lectin pathway of complement activation and its levels are largely determined by frequently occurring polymorphisms of the MBL gene. Our studies show that high MBL levels in the transplant recipient are associated with poorer graft survival and in the case of SPKT also with poorer survival of the recipient. While low MBL levels are associated with better survival we also show that low MBL does increase the risk for infectious complications after SPKT. Properdin is classically described as a stabilizer of the alternative pathway of complement activation. This thesis points towards a new role for properdin by describing a direct interaction with apoptotic cells and with the tubular epithelium of the kidney. By directly binding to these cellular surfaces properdin may contribute to the clearance of apoptotic cells and participate in complement activation and renal damage in proteinuric states.