Three-Gene mRNA Signature IDs Acute Cellular Rejection
WEDNESDAY, July 3 (HealthDay News) -- A signature composed of messenger RNA (mRNA) from three genes in urinary cells can identify kidney biopsy samples showing acute cellular rejection, according to a study published in the July 4 issue of the New England Journal of Medicine.
Manikkam Suthanthiran, M.D., from Weill Cornell Medical College in New York City, and colleagues examined mRNA levels in urinary cells from 4,300 urine specimens from 485 kidney-graft recipients, and correlated them with allograft-rejection status.
The researchers found that a three-gene signature, including CD3ε mRNA, interferon-inducible protein 10 mRNA, and 18S ribosomal RNA was able to distinguish between biopsy specimens showing acute cellular rejection and those not exhibiting rejection (area under the curve [AUC], 0.85). The AUC was 0.74 in an external-validation data set, which was not significantly different to the AUC in the primary data set. The signature was able to differentiate acute antibody-mediated rejection and borderline rejection from acute cellular rejection, with an AUC of 0.78. In addition, the signature distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies, and was able to diagnose acute cellular rejection in both groups of patients. In the group of patients with rejection, there was a sharp increase in the trajectory of the signature in repeated urine samples during the weeks before the biopsy showing rejection.
"In conclusion, the diagnostic signature calculated from the mRNA levels of genes relevant to acute cellular rejection described in this study may provide a direct measure of risk (the predicted probability that a biopsy would reveal acute cellular rejection) and a means of assessing immune status with repeated assessments," the authors write.
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