A Closer Look at Chimerism

A vital organ transplant may seem like the end of a long journey through illness, treatment, and weeks, months, or years of waiting. But, in many cases, a new organ is only the beginning of another lifelong journey of immunosuppression and the constant risk of rejection. The immediate concern after transplant is to avoid acute rejection, a condition that places both the patient and the graft at risk. And though immunosuppressive therapy is an effective treatment for acute rejection, it carries its own set of disadvantages, including nephrotoxicity and the risk of opportunistic infections. What can be done to balance these two competing interests?

Ideally, patients will achieve tolerance – a state in which immunosuppression is not required to prevent rejection of the donor organ. In some cases, it’s possible to induce tolerance in patients; for example, by infusing bone marrow cells from the organ donor into the recipient to establish persistent donor chimerism – the coexistence of immune cells from both donor and recipient in the recipient’s body. What makes this an effective method? Researchers from Northwestern University and the University of Virginia investigated patients with this type of induced tolerance to find out the mechanisms involved (1). Gene expression analysis indicated that, in control patients, T- and B-cell-mediated rejection pathways were upregulated at the molecular level – whereas in tolerant patients, no upregulation was seen. Further analysis revealed the induction of regulatory elements known to downregulate inflammation and maintain tissue homeostasis.

It is the first time the molecular mechanisms of chimeric tolerance have been shown, and the researchers are hopeful that it will improve future patient care. Lead author Lorenzo Gallon believes that the data generated could not only help in the longitudinal monitoring of tolerant patients, but also aid in the identification of patients whose chronic immunosuppression could be minimized (2).