- Dr Candice Roufosse, Principal Investigator
- Prof. Terry Cook, Co-Applicant
- Dr Adam McLean, Co-Applicant
- Dr Jacques Behmoaras, Co-Applicant
- Dr Linda Moran, Associate
- Dr Jan Ulrich Becker, Associate
- Dr Michael Mueller, Associate
- Imperial College, London, UK
- Tissue analysis of biopsies from the transplanted kidney in patients with antibody against their graft - is the antibody being tolerated or causing damage?
After kidney transplantation, some graft recipients develop antibodies against the graft. In some patients, these antibodies lead to rejection of the graft. Although in some cases the damage is detected in the clinic by a loss of graft function, in others, damage can develop slowly and silently, such that once it finally becomes apparent it does not respond to treatment, and graft loss ensues. This phenomenon of "chronic rejection" is the leading cause of late graft loss. It would be useful to identify early markers in patients who are developing such organ damage, in order to modify their drug regimen at a stage where the disease process is responsive. Changes in the cells lining the capillaries in the graft (endothelial cells) and the cells within the capillaries (inflammatory cells) are thought to be crucial for the effect of antibody on the graft. We will study the endothelial and inflammatory cells in the capillaries of kidney biopsies taken from patients using microscopy, and analysing expression of proteins and of messenger RNA, to see if these can help define whether antibody is causing trouble or not. Microscopic appearance will include not just light microscopy, which affords tissue magnifications of up to 1000x, but also electron microscopy, which allows visualisation of the tissue at magnifications up to 10,000,000x. In some patient with antibody, there does not appear to be any damage to the graft - these patients are said to have "accommodated" their graft. This state is the holy grail in transplantation, but so far very few markers exist to identify it. We will attempt to use sensitive new techniques of analysing gene expression to define markers of accommodation in stable patients with antibody. These patients would benefit from having their drugs reduced or removed altogether, in order to avoid secondary effects related to their use. The overall aim of the project is to prolong patient and graft survival, to make best use of the precious donated organs.