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The function of the immune system was critical to survival of our species. Prior to the 20th century man’s greatest killers were, in fact, infectious diseases. It is important to note that not everyone’s immune system functions in the same way because genetic diversity determines how one individual will react to a given infection. Diversity in the immune response has protected us from devastating events. For example, not everyone who got the bubonic plaque died. Some individual had a genetically programmed immune response that was more effective than others and they were able to survive. There are many examples of that throughout history of our species.

Because of this the immune system has to be adaptable enough to identify even infectious agents that hadn’t existed before. The HIV virus is a good example. To generate such enormous diversity, the controls of the immune system are extraordinarily complex. For these reasons, autoimmunitywhich is a malfunctioning of the control of the normal immune systemis also complex and multi-factorial.

A reporter asked me a very important question, “Why should I put an article about pemphigus in my paper since it is such a rare disease and only affects such a few number of people?” Well, the answer is that autoimmune diseases are actually the 3rd most common human ailment behind cardiovascular disease and cancer. The prevalence of autoimmunity has been under-appreciated because many of the diseases are so organ specific that they fractionated to the “turf” of individual specialties. For example, thyroiditis is an endocrine problem. Lupus is a rheumatologic disease. Inflammatory bowel disease is seen by gastroenterologists. Multiple sclerosis is a neurologic disease. However, if you lump all autoimmune diseases together, it is an incredible important problem for our population. Advances in understanding one autoimmune disease can often translate into better understanding of other autoimmune diseases.

What are the key components of the immune system? There are cells that are called antigen presenting cells. These cells ingest and process foreign organisms such as a virus, a fungus, or bacteria which invade the body. They are then presented to the immune system so that the immune system can respond. There are two different kinds of cells that direct the immune response: T-Cells and B-Cells. These are your soldiers of the immune response. T-Cells are the killer cells and the production of protective antibodies is directed by B-Cells. Some B-Cells mature into plasma cells and they produce a serum protein called an antibody. These antibodies then protect you against foreign organisms. For example, when you get a diphtheria shot as a child, you make antibodies against that diphtheria toxin and those antibodies neutralizes any toxin they encounter. These antibodies keep some diseases away.

In pemphigus, the key players are antibodies because the disease and the damage to the skin is caused by antibodies. Not by the killer cells – T-Cells, but by antibody. Actually antibodies look like a little a “Y”. Antibodies directed against the skin attack the skin cells and cause them to fall apart.

The immune system is very specific. Certain cells are programmed to produce certain antibodies. It is kind of a lock and key type recognition system. Antibodies will bind to only those proteins that it is programmed to bind against. In pemphigus, desmogleins (the “glue”) in skin cells are recognized as an invading organism. Anti-desmoglein antibodies are then produced. Pemphigus is difficult to treat and there are known reasons for that. Antibodies in the normal state are directed against invading organisms and are protective proteins. These antibodies are protective proteins with long half lives, and cannot be destroyed because they are not recognized as being harmful to the body. The immune system thinks it is doing “the right thing” by producing autoantibodies against pemphigus antigens.

Antibodies last a long time; they have a half life of about 3 weeks. Once programmed to respond they are very durable. So the disease is not going to respond to treatment rapidly. It takes timetime and a lot of intensive therapy over months and years to try to down regulate that effect. The other problem is that we don’t know how to block the instructions from the immune system that reacts against a single protein, such as to block that one protein against desmoglein.
In PV we know of 2 specific genes that are involved with the disease process. In Jews it is the DR4 gene, and in Northern India, China and Japan it is DQ1. There are also other less frequent genes that can predispose a person to this disease, but these are the key ones.

The basic approaches used to treat pemphigus are: Prednisone, Immunosuppressive drugs, and new therapies like IVIg and Rituximab. However, to date there is nothing that targets the specific protein. The Peptimmune trial drug, if it works, will target the specific protein.

Geplaatst in Medical


The P/P Registry has been approved by the Western Institutional Review Board (WIRB) and is actively enrolling participants.