Sunday, April 22, 2007

B cells keep the autoimmune pot boiling

B cells in mammals have two main purposes. One, they make antibodies to fight pathogens (harmful viruses, bacteria, fungus, protozoans). Two, they retain immune memory of the antibodies needed to win previous pathogen battles.

If B cells incorrectly decide some part of our body is an enemy pathogen, then they make antibodies to label and to destroy it. These antibodies are no different structurally than any other good antibody. Because these antibodies cause attacks on your own tissue, researchers call them autoantibodies.

B cells also retain a memory of how to make these autoantibodies during remissions. B cells keep the autoimmune process going and they can restart it again after it is brought into submission by DMARDS, TNF alpha inhibitors (Remicade, Enbrel, Humira). If the B cells which make the auto-antibodies (and which retain the memoryo how to make them) are not eliminated, then the autoimmune disease you have can never end. Many new medications are on the way to destroy B cells or hinder their ability to make antibodies.

The B cells make the IgG antibodies that label a protein so that dendritic cells and macrophages know what to attack, engulf and destroy. If that protein is in a pathogen, good for you. If that protein is a part of your own body, you have autoimmune disease.

When autoimmune flares occur, these autoantibody producing B cells very rapidly increase. They are born inside your bones in the bone marrow. You may have felt the aching pressure in your wrist and lower leg bones caused by their rapid growth. I know I have.

I remember lying awake at night feeling the tremendous pressure in my wrists and mentally considering whether I could relieve the pressure better by smashing the bone with a hammer or drilling into it with my electric drill. Of course I did neither. Eventually the pain lessened. Apparently the rapidly produced "baby B cells" had left my bone marrow and had gone out to the mucous membranes of my intestinal lining. That migration resulted in less bone pain, but more gut problems.

Here is the URL of an article describing how autoantibodies produced by B cells are the key to the continued propagation of the autoimmune feedback loop:

B cells come in an infinite variety. Most kinds are very beneficial. They are key components of your immune response to pathogens and cancer. Killing all the B cells in your body makes you more vulnerable to infectins and cancer. You will even be vulnerable to childhood infections you previously had immunity to.

Sadly the only B cell medication on the market today is Rituxan which kills all B cells—both autoimmune causing ones as well as life preserving ones. B cell therapies that target only autoantibody producing B cells are still years away.

Rituxan has a very high rate of side effects as it is a mostly mouse protein (30-70%) monoclonal antibody. (Human cancer cells are fused with mouse cells to make it.)

There are fully human B cell killers (monoclonals) on the way. HuMax CD-20 is closest to being approved. Maybe FDA will allow it for RA in a year or two. All other autoimmune suffers must wait another five to ten years for additional clinical trials in order to use the fully human, HuMax CD-20. Our only choice today is to a chance on severe advere reactions and use Rituxan.

Rituxan is a short term answer at best. Almost all humans will eventually have a severe, perhaps, life threatening reaction to the mouse protein. Maybe not the first time or the second, but eventually, your body will notice the mouse protein and your immune system will go nuts. The doctors call that an adverse reaction.

Today you are not allowed to be infused with Rituxan unless you are “prep-ed” first. The prep-ing consists of a strong dose of antihistamine and prednisone. The idea is that if this is your time to react, you already have two of the drugs in your system that are used to try to stop adverse reactions. They are not always successful.

Reactions include gross swelling of body parts, whole body hives, sudden loss of blood pressure to the extent that no oxygen gets to your brain. The scientific terms for this are angioedema, urticaria, and syncope. The whole fun process is called anaphylaxis. It is very often fatal. If you survive the onset of symptoms, plan on these symptoms re-occurring for a month or more. Rituxan has been engineered to have a very long half life in your body.

At the beginning of the twentieth century when transfusions were the rage and doctors did not yet know about blood types, many doctors said, "Blood is blood is blood. If my patient needs blood it does not matter what kind I give him." So they tried giving sheep blood. It was blood after all.

All their patients died from adverse reactions to the sheep proteins in the sheep blood. It took quite awhile for doctors to fully understand that animal blood when transfused into humans, killed the humans. (It is actually our own immune system that kills us by over reacting to the foreign blood proteins.) For that matter transfusing blood from one mammal species to any other would kill the recipient mammal. So vets do not give dog blood to a cat unless they want the cat to die.

Today Big Pharma with a lot of money to be made says, "a monoclonal is a monoclonal is a monoclonal. " Thankfully the FDA is finally requiring black box labeling om some of these mouse monoclonals. Many, many patients have already died first.

Currently much of the FDA budget is provided by Big Pharma, so it takes a lot of deaths before the FDA will warn us of a problem with any blockbuster drug from a large pharmaceutical company.

Remicade is another mouse monoclonal. I see no reason for anyone to use it when Enbrel and Humira are available. Neither Enbrel or Humira has mouse proteins in them. Humira is a fully human monoclonal.

More on B cells later.

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