Kidney Transplant Tolerance “Signatures” Published in Two Separate JCI Reports

May 26, 2010

The results of two Immune Tolerance Network (ITN)-sponsored efforts in identifying genetic and cellular signatures of transplant tolerance were published this week in the Journal of Clinical Investigation. The signatures are patterns of gene expression and cell types that were found to be characteristic of a set of rare patients who developed a natural tolerance for their kidney transplant – meaning they do not require anti-rejection medications. It is hoped that these signatures will one day yield a test that will allow doctors reduce the dose of or even eliminate anti-rejection medications in an individually tailored fashion.

The first team, funded entirely by the ITN, was led by Emory transplant surgeon Kenneth Newell, MD, PhD, as part of the ITN Registry of Tolerant Kidney Transplant recipients. In order to carry out their analysis, Newell and partners identified the largest-ever set of naturally tolerant subjects – those who have stopped all immunosuppression, but have not rejected their kidney transplant. Such patients are exceedingly rare in the world of transplant – in almost all cases, stopping anti-rejection medication results in rejection and loss of the transplant.

Upon analyzing blood specimens donated by these twenty-five patients, Newell and team identified a set of only three genes whose expression levels uniquely identified them from a group of more typical transplant patients who were taking immunosuppression. These three genes were all involved in B cell differentiation, indicating a possibly greater role for this type of immune cell in establishing tolerance than previously thought. The findings were backed up by elevated levels of certain B cell subsets found in the tolerant subjects.

The second team, funded by the ITN and other European partners, managed to identify a cohort of eleven naturally tolerant subjects for their study. The group found that, in comparison to typical transplant subjects on immunosuppression, tolerant subjects displayed increased levels of B cells as natural killer cells, as well as a number of other differences that uniquely identified these patients.

The two teams validated each other’s findings by sharing samples from each other’s groups of patients.

The teams are now planning follow-up studies that will eventually seek to establish whether these signatures may be used to prospectively reduce or eliminate immunosuppression in some individuals following kidney transplantation.

Warning: Under no circumstances should kidney transplant recipients reduce or stop taking prescribed anti-rejection medications without the consent and direct supervision of their doctor. Doing so will almost certainly result in long-term consequences to their health, including the loss of the transplanted kidney.

More Information

Newell KA, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. Online First.  doi:10.1172/JCI39933 .

Sagoo P, et al. Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest. Online First. doi:10.1172/JCI39922 .

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