Saturday, March 10, 2012

A Small (but Promising) Pilot Study: Reducing Organ Rejection

Your immune system is responsible for recognizing and fighting off invaders that cause illness.  However, what if you needed your immune system to make an exception for particular foreign cells?  This is the challenge that organ transplant recipients face.  If their body rejects their new organ, they face a repeat transplant or possibly death.  To prevent this rejection, doctors attempt to find a donor organ that matches the recipient’s original organ, so that their immune system is less likely to detect the new organ cells as unfamiliar.  Recipients also have to follow a very expensive, strict drug regimen for the rest of their lives to suppress this potentially devastating reaction to the new organ.  A new pilot study may reveal a different treatment for organ recipients that would decrease the rejection rate and relieve recipients of a lifelong reliance on anti-rejection drugs.

The adaptive immune response is responsible for organ rejection.  This branch of the immune system is a delayed specific reaction to a foreign cell, as opposed to the innate immune response, which is a general immediate reaction to any foreign object.  Rejection mechanisms are broken down into two parts of the adaptive immunity, cellular immunity and humoral immunity.   
Cellular immunity involves the activation of immune cells in the body.  On immune cells, like white blood cells, there is a surface molecule called the major histocompatibility complex (MHC).  This molecule is what determines a ‘match’ for organ donors.  MHC is highly variable among people, and cells that do not have the same MHC are easily identified as foreign.  These different donor cells are attacked by recipient immune cells.

Humoral immunity involves antibodies which mark the foreign cells for destruction.  If the recipient had previously come in contact with some other mismatch, such as being given the wrong blood type, these antibodies will be readily available to identify the foreign cells. 

This small pilot study involved eight patients who received new kidneys.  All of the kidneys were a less than perfect match based on MHC elements.  This mismatch scenario is common in organ transplants and the challenge becomes keeping the organ healthy and preventing rejection.  Usually, after the surgery, these patients would need to take anti-rejection drugs for the rest of their lives to prevent rejection.

However, this study used a different approach to trick the immune system into accepting the new kidney.  First, the patients were exposed to a few days of chemotherapy to suppress their immune response.  Then, a few days after the surgery, the patients received treated adult stem cells from the kidney donors.  The procedure is very similar to a bone marrow transplant.  This introduced immune cells from the donor that would be less likely to attack the kidney.  The cells had room to multiply because of the chemotherapy treatment that occurred before the transplant.  Twenty months after the transplants, five of the patients have been weaned off of anti-rejection drugs and have no rejection symptoms.

Though these results are exciting, they are still very preliminary.   These five patients reacted positively to this treatment, but there is no way to know if the majority of people would also react this well.  There could also be a danger in suppressing the immune system and waiting for it to recover from the chemotherapy. 

Despite the uncertainties, these five patients’ positive responses to the therapy may be the beginnings of an important development in organ transplants.  Being able to use less perfectly matched organs would increase the pool of potential organs for each recipient.  Authors of this pilot study are protecting their commercial interest in this therapy by keeping the exact way that the adult stem cells were identified and treated a secret.  Hopefully follow up studies will have similar success, and this treatment can develop as an effective therapy for organ transplant patients.

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