Biomarkers May Improve Rejection Following an Organ Transplant

Some genetic variants have the potential to affect responses to immunosuppressive drugs that influence organ rejection.

Biomarkers have the potential to aid new approaches for monitoring immunosuppressive drug therapy in patients who have received an organ transplant. A recent study found biomarkers can also help reduce organ rejection and side effects through individualized therapy.

“With current treatment regimens, a relatively high proportion of transplant recipients experience under-immunosuppression or over-immunosuppression,” said lead study author Mercè Brunet, PhD.

The balance between immunosuppression is important. If there is too little immunosuppression, it can lead to an increased risk of transplant rejection, while too much can lead to the development of infections or side effects.

For the study, a panel of 19 international experts analyzed data on a variety of biomarkers.

“Biomarkers should help to tailor immunosuppressive therapy to the needs of the individual patient,” the expert committee said in a press release.

The panel sought to identify biomarkers with “documented and clinical utility” in individualizing immunosuppressive therapy after organ transplantation.

The findings of the study, published in Therapeutic Drug Monitoring, included consensus statements on 4 major categories of biomarkers: biomarkers to assess the risk of rejection; biomarkers of individual response to immunosuppressants; pharmacogenetics markers; and biomarkers of graft dysfunction and injury.

The protein cytokines have important immune functions, such as interferon-gamma or interleukin-2, and seem to be useful in assessing the risk of transplant rejection. Regulatory T cells (Tregs) also have the potential to be useful assessing rejection risk.

Certain biomarkers could have differentiating individual responses to specific drugs. NFAT-regulated gene expression could also have differences in the susceptibility of immunosuppressive drugs, which could allow for the use of a lower dosage in patients.

Additionally there are certain genetic variants that have the potential to affect responses to immunosuppressive drugs. If a patient is administered the drug tacrolimus, commonly used to prevent transplant rejection, the type of CYP3A5 gene could have an effect on the required dose.

Furthermore, biomarkers of graft dysfunction and injury can provide useful information on the function of the transplanted organ. Although, there is not a single test that can show the complexities associated with organ transplantation, a “comprehensive panel of distinct biomarkers” could be useful in monitoring and individualizing immunosuppressive treatment, the panel concluded.