Proteome Sciences has applied its ProteoSHOP® technology to clinical samples from heart transplant patients with acute and chronic rejection (diagnosis confirmed following biopsy analysis) through a collaboration with The Heart Science Centre at Harefield Hospital, Imperial College, London. Two-dimensional gel electrophoresis (2DE) has revealed differences in the protein expression profiles between rejecting and non-rejecting patients; mass spectrometry has been used to identify the relevant proteins which have been validated in immunoblot/ELISA methods. Blood biomarkers for acute and chronic rejection have been discovered, and these techniques are now being applied to renal and potentially other transplant patients.

Acute Rejection

Acute rejection occurs 3-6 months after transplantation. Constant vigilance is required to monitor the immune response to the grafted organ. An initial panel of 13 protein markers of acute rejection was identified during a longitudinal study of heart transplant patients. ELISA assays have been successfully developed for 3 of these proteins to date, with the others in development.

Chronic Rejection

Chronic rejection, occurring at least 6 months after transplantation, is very difficult to diagnose clinically and usually presents as a gradual vasculopathy of grafted vessels.

Transplant-associated coronary artery disease (TxCAD) is the most important complication after the first year of cardiac transplantation, with an incidence of 40% at 5 years post-transplant. A study was undertaken involving sequential samples collected from 109 heart transplant patients up to 5 years after transplantation. A novel protein marker has been identified in patient sera that has utility as an independent predictor of TxCAD, and can be used to identify patients at high risk of developing this complication. An ELISA has been developed to detect this protein in patient blood samples.

Partnering

Proteome Sciences is seeking partners to accelerate the development and commercialisation of its proprietary markers for chronic and acute rejection by way of license and/or strategic alliances and to develop further applications for the technology. Other than acute and chronic rejection after heart transplantation, a major initiative is underway to address rejection in kidney transplantation in recognition of the increased level of costs and trauma associated with dialysis and the potential future opportunities offered by xenotransplantation.