MicroRNA Expression Levels are Predictive of Human Allograft Status

Dr. Manikkam Suthanthiran of the Weill Cornell Medicine has identified several miRNAs that are overexpressed in allograft rejection and could serve as biomarkers of acute allograft rejection, as well as allograft function.

Transplant recipients require life-long treatment with nonspecific, toxic, and multiple immunosuppressive drugs and are forever under the threat of losing their allografts because of immune rejection of the transplanted organ. Emerging data suggests a critical role for miRNAs in the regulation of immune cell development and in the modulation of innate and adaptive immune responses.

Dr. Suthanthiran investigated whether acute rejection (AR) is associated with alterations in miRNA expression within allografts, and whether expression profiles are diagnostic of AR and predict allograft function. This lab has found that acute rejection of human renal allografts is exemplified by increased expression of specific miRNAs, correlating with expressions of activated immune cells, which infiltrate into the allograft causing AR. In addition, acute rejection of human renal allografts was also characterized by underexpression of some miRNAs within the rejecting allografts compared to allografts with normal biopsy results. Measuring the expression levels of specific miRNAs from biopsy samples of transplanted kidneys, both normal and those experiencing AR, these scientists showed that such expression levels could predict acute rejection with sensitivity & specificity both > 90%.

In summary, acute rejection is associated with significant alterations in the expression of specific miRNAs within allografts, and intragraft miRNA expression patterns are diagnostic of acute rejection and can predict renal allograft function. Therefore miRNA expression levels found in blood, tissue or urine samples can serve as biomarkers of human renal allograft status.