Sunday, October 5, 2014

In the NEWS: FSGS and CD40- a potential new finding

A new potential culprit might have been found for the recurrence of FSGS post transplant. A recent article evaluated pathogenic antibodies in 141 serum samples over 64 patients and looked at many potential culprits such as CD40, PTPRO, CGB5.etc and pre transplant elevation of anti CD40 alone was the best predictor of FSGS recurrence after transplantation.  Another study highlight is the observation that patient-derived antibodies against CD40 functionally cooperate with a previously identified culprit of FSGS called soluble urokinase plasminogen activator receptor (suPAR). Co-injection of patient-derived CD40 anti-autobodies and suPAR caused enhanced kidney filter failure more than each component did by itself.

This is fascinating as can anti CD40 therapies then lead to preventing FSGS in kidney transplantation?

Abatacept or belatacept may have some role in FSGS treatment. A recent study showed the success of using such agents in minimal change disease. It is interesting to note that in presence of cd40 auto antibody, the wild type suPAR becomes pathogenic to the podocyte.  There seems to be an on/off switch for suPAR perhaps with Cd40 and a trial of belatacept in FSGS might be warranted.  

Would co stimulating blockade agents be sufficient as their interaction as an anti CD40 is possible?- as we use those in transplant anyway? Perhaps, looking at the recurrence of FSGS in patients on belatacept might be a good start.  Or are we specifically going to look at ant CD40 agents( some of which are being studied as anti cancer agents in colon cancer and others)

There is some data of use of this agent in panc transplantation as well.

For full paper look here

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