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Quantification of transplant-specific DNA in plasma for the early detection of rejection reactions

For whom is TheraSure-TRANSPLANT MONITOR test suitable?

Patients after organ transplants are under constant control of organ function and immune status. Immunosuppressive drugs suppress the body's defense, which is necessary, but of course also risky. Often functional damage of transplanted organs is recognized too late. The TheraSure-TRANSPLANT MONITOR-Test detects organ damage at the earliest possible time point, which can allow for the saving of the organ.

What does the test reveal?

There are decision limits for the course of various organ transplants (kidney, liver, heart). If the measured value is significantly higher, there is a transplant damage that needs to be further investigated. Or if a continuous increase is observed in follow-up control, an accurate diagnostic clarification of the cause should be made. Since the determination is entirely specific to the graft, an increased value always indicates an increased cell death in the organ, e.g. caused by sub-immunosuppression.

Which standard of care monitoring is done after transplantation?

Patients after organ transplantation are under constant control of organ function and immune status. Particularly, the determination of the concentration of immunosuppressive drugs is standard today and is carried out very regularly. The suppression of the body's defense, which would quickly destroy the foreign organ, is imperative. Recognizing a rejection so early that serious damage can be avoided is very difficult with the existing methods. A functional limitation of a kidney transplant is that rejection of the transplant by the patient (organ recipient) is only recognized if at least 50% loss of function has already occurred. The determination of the immunosuppressive drug concentration is helpful to avoid side effects and overdoses, but is of limited usage for measuring the effectiveness of the immunosuppressive effect. A constant high dosage of the immunosuppressive drug is not possible, since this leads to long-term damage to, for example, the kidney.

Anny immunosuppression must always be as high as necessary to control rejections and as weak as possible to minimize serious side effects and drug toxicity.

What is the risk of rejection?

Rejection is a reaction of the body's defense against foreign tissue or foreign cells. The immune system recognizes this tissue as foreign and tries to eliminate the supposed foreign material. For this purpose, cells in the blood circulation are activated to attack the foreign tissue. In consequence, a destruction of the graft threatens, to a lesser degree a functional restriction. It is assumed that even subliminal (not easily recognizable) rejection reactions in the long run lead to transplant loss and therefore influence the survival time of the organ.

How does the test work?

First, a blood sampling is taken in a special tube and sent to the laboratory. There, the plasma is recovered, and the concentration of the transplant DNA is determined therein. This analysis takes two days for the first determination, and one working day for each additional sample of an already known patient.


What is cell-free DNA?

DNA is the genetic substance stored in each cell, which is unique for every human being. Nevertheless, all cells of the body have an identical copy of this DNA, which is inherited in half from your father and mother. Cells in the bloodstream and in organs release this DNA to the environment within the scope of normal cell death. Thus, such DNA enters the liquid portion of the bloodstream called blood plasma. Although the concentration is low, this free DNA can be detected with today's technology.

The highly sensitive TheraSure-TRANSPLANT MONITOR already detects a rejection reaction in the early stages and thus allows therapeutic intervention before possible irreversible damage or even an entirely pronounced rejection can occur.

How can cell-free DNA be used in transplant monitoring?

A transplant places a second DNA from the transplanted organ into the body and, that DNA is clearly distinguishable from patients DNA. Even in a transplant, cells always naturally die, and are then replicated. Therefore, cell-free DNA from the transplanted organ can always be detected in the blood plasma. In case of damage to the graft, e.g. by a rejection reaction, many more cells die off, leading to a significant increase in the DNA from the transplanted organ in the plasma. This provides a new value which is entirely specific to the transplanted organ and which can be measured with high sensitivity and accuracy.

What is the advantage of the TheraSure-Transplant Monitor?

The advantage of the test is that it is absolutely specific for the transplanted organ and that has a very high sensitivity. The latter means that, e.g. the suspicion of rejection can be remarked at a very early stage. Several studies, by us and other scientific working groups, have shown for cardiac transplants in the chronic phase (> 3 months) that a continuous increase in cell-free transplant DNA can precede the subsequent clinical rejection diagnosis by weeks. The advantage for the patient is thus the detection of early warning signs, which allow for a therapeutic intervention before possible irreversible damage occurs due to a full blown rejection of the organ. Biopsies can be saved due to the high negative predictive value for rejection and transplant damage.

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