A potential biomarker of tolerance in kidney transplant recipients was found to be stable for up to three years in a cohort of 32 operationally tolerant kidney recipients from the ITN’s FACTOR study. The signature is characterized by the increased expression of two genes associated with B cells, suggesting a potential role of B cells in regulating the immune response to the kidney. The results were reported on October 13th in the American Journal of Transplantation.
Long-term use of immunosuppressive drugs in transplant recipients is associated with significant adverse events such as increased risk of malignancy and other toxicities. A small percentage of kidney transplant recipients have been able to successfully come off immunosuppression without rejection, and an important goal of tolerance research is to identify biomarkers that can help predict individuals who may be able to safely wean from medication.
The ITN’s FACTOR Study of Tolerant Kidney Transplant Recipients identified a B-cell-specific gene signature that was associated with tolerance in a registry of 25 kidney transplant recipients who had been off immunosuppression for at least one year and were considered to be ‘operationally tolerant’ (results were reported in 2010). This B cell signature was able to distinguish tolerant individuals from kidney recipients still on standard immunosuppression.
The data published last week in AJT confirmed the presence of this B cell gene signature in seven additional tolerant kidney recipients recruited to the registry since the time of first publication, and that the signature remained stable after three years. There were, however, a few individuals in the standard immunosuppression group that showed an increase in the tolerance signature over time, the cause of which is still speculative.
A more in-depth analysis of B-cell populations also revealed that tolerant individuals had increased frequencies of total, transitional, and naïve B cells compared to the standard immunosuppression group, but conversely had fewer memory B cells. These results warrant further studies to determine the utility of the B cell gene signature and B cell profiling for assessing tolerance.