Biomarkers are always a hot topic in transplantation. At the ATC, Dr. Barbara Murphy, from the Icahn School of Medicine at Mt. Sinai, gave an intriguing discussion on molecular biomarkers developed as part of the GoCAR study.
To set the stage she confirmed that current clinical assessment of risk factors for rejection and long term graft outcome are extremely limited. During periods of allograft dysfunction a biopsy is the only current method of determining cause. However, biopsies are invasive, somewhat subjective, reactive, limited by sampling, and require arbitrary cutoffs. Molecular profiling may be able to enhance diagnostic accuracy of biopsies, and allow non-invasive methods of making a diagnosis.
The GoCAR study (genomics of chronic allograft rejection) was a multicenter study where clinical parameters were collected and molecular profiling was performed in protocol biopsy tissue and in peripheral blood mononuclear cells. Below are the salient points of her study.
They attempted to discover genes present in 3 month protocol biopsies which would predict scarring in 12 month biopsies. They found a 13 gene set which predicted biopsy score at 12 months with an average AUC of 0.947.
These genes also predicted biopsy score at 24 months and graft loss.
When looking at peripheral blood they discovered 4 micro RNA signatures which predicted graft loss especially when combined with clinical parameters of risk.
They were able to predict which patients develop subclinical rejection and borderline rejection which have been associated with graft loss.
To conclude, her group is now attempting to use this data to identify genes that propagate graft fibrosis and develop novel therapeutics to intervene and improve long term outcomes. Hopefully further studies in the near future will make this type of molecular profiling available to aid in clinical decision making. More to come in the future!
Post written by Dr. Vinay Nair, AJKD Blog Advisory Board member.
Check out more AJKD blog coverage of the 2015 American Transplant Congress.