Biomarkers and a tailored approach for immune monitoring in kidney transplantation

A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers,all in the quest for the much sought after-but perennially elusive-"holy grail" of kidney biomarkers able to unequivocally predict acute transplant rejection vs non-rejection.Detection methodologies and study designs were many and varied.Hence the motivation for this editorial,which espouses the notion that in today's kidney transplantation milieu,the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single "omniscient" biomarker.In addition,we desire to direct attention toward greater scrutiny of biomarker publications and decisions to implement biomarkers in practice,standardization of methods in the development of biomarkers and consideration for adoption of "biomarker-driven" biopsies.We propose "biomarkerdriven" biopsies as an adjunctive to and/or alternative to random surveillance(protocol) biopsies or belated indication biopsies.The discovery of a single kidney transplantation biomarker would represent a major breakthrough in kidney transplantation practice,but until that occurs-if ever it does occur,other approaches offer substantial potential for unlocking prognostic,diagnostic and therapeutic options.We conclude our editorial with suggestions and recommendations for productively incorporating current biomarkers into diagnostic algorithms and for testing future biomarkers of acute rejection in kidney transplantation.

Histopathological analysis of infiltrating T cell subsets in acute T cell-mediated rejection in the kidney transplant

AIM To compare the differential immune T cell subset com-position in patients with acute T cell-mediated rejection in the kidney transplant with subset composition in the absence of rejection, and to explore the association of their respective immune profiles with kidney transplant outcomes.METHODS A pilot cross-sectional histopathological analysis of the immune infiltrate was performed using immunohistochemistry in a cohort of 14 patients with acute T cellmediated rejection in the kidney transplant and 7 kidney transplant patients with no rejection subjected to biopsy to investigate acute kidney transplant dysfunction. All patients were recruited consecutively from 2012 to 2014 at the Singapore General Hospital. Association of the immune infiltrates with kidney transplant outcomes at up to 54 mo of follow up was also explored prospectively.RESULTS In a comparison to the absence of rejection, acute T cell-mediated rejection in the kidney transplant was characterised by numerical dominance of cytotoxic T lymphocytes over Foxp3^+ regulatory T cells, but did not reach statistical significance owing to the small sample size in our pilot study. There was no obvious difference in absolute numbers of infiltrating cytotoxic T lymphocytes, Foxp3^+ regulatory T cells and Th17 cells between the two patient groups when quantified separately. Our exploratory analysis on associations of T cell subset quantifications with kidney transplant outcomes revealed that the degree of Th17 cell infiltration was significantly associated with shorter time to doubling of creatinine and shorter time to transplant loss.CONCLUSION Although this was a small pilot study, results support our suspicion that in kidney transplant patients the immune balance in acute T cell-mediated rejection is tilted towards the pro-rejection forces and prompt larger and more sophisticated studies.