I meant to include this in the previous post but forgot.
Another interesting thing is that being on immune suppression drugs after having an organ transplant drastically raises the chances of developing some (but not all) cancers. In particular, we see the sort of cancers that are a product of chronic viral infection and genomic irritation. Squamous cell carcinomas of the skin are a big one. Women can get these in their cervix from HPV; immune suppression makes everyone all the more vulnerable to HPV. Other viruses, like Epstein-Barr that healthy people will clear without a problem, will fester in the body and provoke the development of lymphomas and the like.
The fact that some cancers appear in light of a weakened immune system but not others is a useful demonstration of the fact that we really don't know what causes cancer in every case. Sometimes it seems environmental; enough radiation and anyone will get cancer; smoking cigarettes can cause lung cancer too. Cancer can be caused by infection: transplant patients get lymphomas and squamous cell carcinoma; AIDs patients get characteristic neoplasia (cancer) as well. Genetic deficiency of appropriate anti-cancer genes (BRCA mutation, hereditary adenopolyposis coli, other familial cancers) can be a cause. Maybe bad luck has something to do with it too.
Showing posts with label transplant. Show all posts
Showing posts with label transplant. Show all posts
Friday, June 24, 2011
Wednesday, June 22, 2011
The yin and yang of immunology
One of the tricky things about cancers is that they have figured out how to evade the police force of the body, the immune system. The immune system should destroy cancer cells, and yet obviously it doesn't always. How exactly cancer cells figure out how to evade the immune system is something that is being extensively studied. The goal of cancer immunotherapy is to re-train the body's immune system to target and destroy cancer. The best model for this is melanoma, a lethal form of skin cancer. Right now, the best option to treat metastatic melanoma in humans is essentially to infuse patients with IL-2 (the immune equivalent of cocaine-laced red bull) and hope for the best. With IL-2, the body's immune system changes from a local sheriff and his deputies to a full-fledged SWAT team. The immune-swat team still isn't sure what it is hunting for, but it ends up killing a lot, including the cancer if the patient is fortunate. (Giving the swat team specific cancerous targets is the ultimate goal.)
Transplantation immunology is precisely the opposite. Instead of encouraging the immune system to attack the tissue in question, we are doing everything in our power to hold the immune system back. This can be accomplished by drugs which prevent lymphocytes (immune cells) from replicating, block signaling and stimulation, or just kill the lymphocytes outright. Obviously, if the police force is eliminated then a lot of criminals will end up running around; transplant patients are chronically dealing with infections (especially viruses like CMV, HSV, and EBV). Despite these immune-destroying efforts, chronic rejection of transplanted organs by poorly understood mechanisms seems almost inevitable. In humanity's defense, huge strides have been made in dealing with acute transplant rejections, which occur through better understood mechanisms.
It is really interesting if one thinks about it: cancer cells have figured out how to avoid immune destruction, and so the answer to better transplantation immunology is potentially right in front of us and we just can't see it. Another interesting scenario is this: if we took a kidney from a child and transplanted it into the child's mother, the mother would reject the kidney unless appropriate immunosuppressive drugs were given (as in any other case). How then did that child manage to survive in the mother's womb in the first place? Why did the mother's immune system not immediately attack the fetus and destroy it?
The answer is lots of theory backed by some evidence, much of it conflicting. This is the same state of affairs as most other things in medicine. Humility makes a whole lot of sense.
Transplantation immunology is precisely the opposite. Instead of encouraging the immune system to attack the tissue in question, we are doing everything in our power to hold the immune system back. This can be accomplished by drugs which prevent lymphocytes (immune cells) from replicating, block signaling and stimulation, or just kill the lymphocytes outright. Obviously, if the police force is eliminated then a lot of criminals will end up running around; transplant patients are chronically dealing with infections (especially viruses like CMV, HSV, and EBV). Despite these immune-destroying efforts, chronic rejection of transplanted organs by poorly understood mechanisms seems almost inevitable. In humanity's defense, huge strides have been made in dealing with acute transplant rejections, which occur through better understood mechanisms.
It is really interesting if one thinks about it: cancer cells have figured out how to avoid immune destruction, and so the answer to better transplantation immunology is potentially right in front of us and we just can't see it. Another interesting scenario is this: if we took a kidney from a child and transplanted it into the child's mother, the mother would reject the kidney unless appropriate immunosuppressive drugs were given (as in any other case). How then did that child manage to survive in the mother's womb in the first place? Why did the mother's immune system not immediately attack the fetus and destroy it?
The answer is lots of theory backed by some evidence, much of it conflicting. This is the same state of affairs as most other things in medicine. Humility makes a whole lot of sense.
Monday, June 20, 2011
A way to cut everyone on the liver waiting list
Kidney transplantation, as it compares to liver transplantation, strikes me as a much lower stress affair. For starters, there are more kidneys than there are livers available for transplant (although this is somewhat negated by the fact that more people need kidneys than livers). More importantly, we can keep people alive who have no kidney function via dialysis. This affords time to search for an organ that is a really good match for the recipient. A good match minimizes immune differences (we focus on major antigens like ABO and HLA) and results in a longer lifespan of the graft (transplanted organ).
People with serious liver failure really cannot be kept alive without a transplant. The kidneys and the liver both perform a similar function: filtering toxins from the blood (among other things). Kidneys filter out substances that are ionic or polar; the liver deals with things that are not polar, or fat-soluble. Its been fairly easy for humans to develop a device that can separate ionic substances (dialysis machines) but not so easy to develop an artificial liver.
Anyhow, we can figure out in advance who will need a liver transplant and start looking for an organ for them before time runs out. The way this is accomplished is through a system (MELD) which accounts for a bunch of different factors, including some labs that assess liver and kidney function, as well as time spent waiting. The system works so that people who are closest to the end of their liver function get pushed up on the list.
One of the things that can happen with any organ transplant is a hyper-acute rejection. When this happens, the body's immune system launches an immediate attack on the new organ and the vessels end up getting clotted off and blocked. The only solution to this disaster is to remove and discard the transplanted organ. If this happens to a patient who is receiving a kidney transplant, that is bad, but at least the patient can leave and go back on dialysis. What happens if it happens to a liver transplant patient? There is no substitute.
Turns out, what happens is the patient gets moved to #1 on the national registry for livers. A new liver will be procured from somewhere in the country and delivered to the hospital within a matter of hours.
People with serious liver failure really cannot be kept alive without a transplant. The kidneys and the liver both perform a similar function: filtering toxins from the blood (among other things). Kidneys filter out substances that are ionic or polar; the liver deals with things that are not polar, or fat-soluble. Its been fairly easy for humans to develop a device that can separate ionic substances (dialysis machines) but not so easy to develop an artificial liver.
Anyhow, we can figure out in advance who will need a liver transplant and start looking for an organ for them before time runs out. The way this is accomplished is through a system (MELD) which accounts for a bunch of different factors, including some labs that assess liver and kidney function, as well as time spent waiting. The system works so that people who are closest to the end of their liver function get pushed up on the list.
One of the things that can happen with any organ transplant is a hyper-acute rejection. When this happens, the body's immune system launches an immediate attack on the new organ and the vessels end up getting clotted off and blocked. The only solution to this disaster is to remove and discard the transplanted organ. If this happens to a patient who is receiving a kidney transplant, that is bad, but at least the patient can leave and go back on dialysis. What happens if it happens to a liver transplant patient? There is no substitute.
Turns out, what happens is the patient gets moved to #1 on the national registry for livers. A new liver will be procured from somewhere in the country and delivered to the hospital within a matter of hours.
Subscribe to:
Posts (Atom)