Molecular markers of rejection and tolerance: lessons from clinical research

In terms of finding specific molecular markers associated with graft outcome, attempts have been made to study whole genome transcripts using microarray assays or to study the effect of number of genes of interest using quantitative real-time polymerase chain reaction. Using these techniques, molecular phenotypes of rejection have been characterized, and the variability of the clinical outcome besides similar morphology explained in part. Recently, several specific transcripts including naïve B cell regulation have been identified in the peripheral blood of operationally tolerant kidney transplant recipients. The decrease in immature B cell-related transcripts in the peripheral blood in patients with immunosuppression was shown to be associated with acute rejection. Similarly, tolerance-associated antigen 1 transcripts were identified in biopsies and regulatory T cell transcripts in urine and biopsies in patients without rejection. Better understanding of molecular processes associated with allograft rejection or alloantigen hyporesponsiveness/tolerance may help to improve our knowledge about graft pathology and identify novel markers suitable for future monitoring and guided therapy and finally improve the outcome of kidney transplantation.