New results highlight potential therapy to stop kidney transplant rejection
In a recent study, published in Nature Scientific Reports, our researchers at Imperial College London have shown that a drug that is already in use for other conditions may be an effective therapy to prevent antibody-mediated rejection of transplanted kidneys.
Our immune systems can cause a kidney transplant to fail
One of the main reasons why a kidney transplant might fail is because the recipient’s immune system attacks the transplanted tissue. This is called ‘antibody-mediated rejection’.
If a patient who needs a transplant has been exposed to foreign tissue types, for example during pregnancy, or if they have had an incompatible blood transfusion or previous organ transplant then they will develop antibodies against the tissue types that are not their own. Patients with exceptionally high antibody levels that react to foreign tissue are referred to as ‘sensitised’, and this makes it harder to find a suitable match for transplant, meaning patients are likely to be on dialysis and waiting for transplant for a long time.
There are some treatment strategies available to reduce a patient’s antibody levels prior to transplant but these do not work well and can have nasty side effects. New solutions are desperately needed.
New strategies to combat antibody-mediated rejection
With our funding, as part of our Making Every Kidney Count campaign, Professor Fred Tam and his team at Imperial College London have been investigating a novel way to tackle antibody-mediated rejection.
Fred and his team have discovered that there appears to be more enzyme, called ‘spleen tyrosine kinase’ in rejecting transplanted kidneys, compared to normal kidneys, and these have previously been shown to be involved in stimulating the immune system in several autoimmune diseases.
There is a known treatment called fostamatinib which can turn off this enzyme, and this is currently used as therapy in other disease areas.
In this study, Fred and the team have tested whether fostamatinib could reduce the levels of antibodies in an animal model where animals had been sensitised using blood transfusion.
Early results are promising
Fred explained: “Our results showed that early treatment (24 hours after blood transfusion) with fostamatinib prevented the production of these incompatible antibodies in the preclinical model. When the treatment with fostamatinib was delayed for 7 days, there was still small reduction in antibody level.”
Although this work is still in the pre-clinical laboratory testing stages, it suggests that fostamatinib might provide a much-needed therapeutic option for patients who are at risk of developing high levels of antibodies after blood transfusion while they are waiting for a kidney transplant, increasing their chances of finding a suitable match and having a successful transplant.
Fred and the team also have an ongoing pilot clinical trial to study the effect of fostamatinib in patients with kidney transplants to see if it helps to treat rejection.
Fred said: “It will be important to investigate whether early treatment with SYK inhibitor may be useful in reducing the production of tissue type incompatible antibodies in potential transplant recipients, so that more patients may be offered kidney transplantation.”
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