Diagnostic Markers of Graft Rejection
A major research focus within the TRG has been in the identification of reliable and accurate predictors of rejection. The current technique used to diagnose lung allograft rejection requires histological analysis of transbronchial biopsy tissue. This utilises an invasive and expensive procedure, and still remains unreliable.
As such many research groups have attempted to identify a clinical biomarker of graft rejection. To date there has been limited success in this area, due to lack of specificity or sensitivity. We have identified a very specific and sensitive molecule (coded mX) that can accurately predict an episode of graft rejection within a 6 day period. mX is stable at room temperature and can be detected in small volumes of systemic blood. We are validating the use of patient blood collection via fingerprick and sample postage. This would allow us to clinically survey graft rejection, without the need for out-patient hospital visits. In conjunction with mX, we are validating infection biomarkers (procalcitonin, neopterin, and monocyte HLA-DR to name a few) to establish an infection/rejection multi-test system.
Following validation, we plan to design a ‘home test’ kit utilising commonly used immunoassay technology. The final part of this study aims to describe the biological role of mX in lung allograft rejection. We believe mX is secreted in response to tissue injury, and may prevent tissue death and immune activation. We have already identified that this molecule inhibits T cell activation and alveolar epithelial apoptosis in vitro.
This study was awarded an NHS innovations award, and is funded by an investigator grant from Novartis Pharmaceuticals and a project award from the NewStart Charity. Collaborators include Brian Keevil, Principal Biochemist at UHSM and Marc Clancy, Consultant for Renal Transplantation, Glasgow Western Infirmary.