An article published today in the American Journal of Transplantation examined the prevalence of a previously identified genetic signature associated with tolerance in a cohort of kidney transplant patients who may benefit from immunosuppression minimization. A transplant recipients’ lifetime use of immunosuppressive drugs to prevent rejection exposes them to health complications associated with drug toxicity and long-term immunosuppression. However, the development of grafted tissue tolerance, either spontaneously or intentionally induced, in some kidney transplant recipients suggests that continued immunosuppression is not always necessary to protect the transplanted organ. As significant incidence of damage to the grafted tissue can occur during minimization or withdrawal of immunosuppression, markers of immune tolerance would be useful in informing safe drug withdrawal in tolerant patients, while protecting non-tolerant patients from unneeded risk. In previous studies, ITN reported increased expression of B cell associated genes in tolerant (spontaneous and induced) kidney transplant recipients that was associated with changes in the frequencies of specific B cell populations and stable. In order to test this “B cell signature” in a clinical setting, the ITN and the Clinical Trials in Organ Transplantation (CTOT) consortium designed the ARTIST clinical trial a multi-center observational study with 248 enrolled stable renal transplant recipients receiving immunosuppression. Peripheral blood collected at three specific time-points one year apart was analyzed for the prevalence and stability of the B cell signature.
The current study found the B cell signature in 25-30% of enrolled patients at least once following transplantation and in almost 14% of patients evaluated at all three time points. These patients not only had increased B cell counts but also showed higher expression of the tolerance signature per each B cell. Interestingly, the frequency of the tolerance signature varied in recipients taking different immunosuppressive agents. Although the study did not investigate the association of the B cell signature and tolerance, the authors found that enrolled patients who displayed the B cell tolerance signature at all three tested time points had superior renal function regardless of immunosuppressive regimen.
The reported frequency of the B cell signature indicates that it may be a useful tool for monitoring tolerance in renal transplant recipients. The study also demonstrates that the choice of immunosuppressive agents influences the expression of immune response genes in B cells. Further studies are required to validate these findings and determine if the role that immunosuppressive drugs have on B cells is independent of, or linked to, any effect on the immune status of the transplanted kidney.