Clinical Trials with IVIG and Cyclophosphamide

One of the newest treatments for pemphigus is intravenous immunoglobulin (IVIG). Immunoglobulins are one of the major classes of proteins in blood. IVIG is collected from normal blood donors, pooled, highly purified, and treated to destroy viruses and bacteria. IVIG is now used to treat a number of autoimmune diseases including pemphigus.

There are two particularly attractive features of IVIG as a treatment for pemphigus:

  1. It can rapidly control active pemphigus without resorting to increasing steroid doses, in many but not all patients.
  2. It is unique in being able to selectively decrease blood levels of pemphigus antibodies (the antibodies that cause the disease) without lowering the level of normal antibodies. This feature of IVIG is very desirable, and unique, as all other treatments for pemphigus interfere with the production of all antibodiesthe good along with the badresulting in unwanted side effects.

IVIG appears to work by speeding the degradation or inactivation of all antibodies in blood  the good with the bad. Then, the normal antibodies are replaced by those present in the IVIG that is administered, whereas abnormal antibodies are absent in IVIG and so they are not replacedonly they remain reduced following IVIG.

Complicating this story is that a regulatory mechanism in the body maintains constant levels of each individual antibody in the blood. Decrease in blood level of any antibody (including the pemphigus ones) stimulates new production of that antibody, and a rebound in their levels in the blood. Thus, even though IVIG can decrease serum level of pemphigus antibodies, these will go right back up shortly after the procedure.

This rebound can be minimized, in animals, by administering a cytotoxic drug that blocks the cells that make new antibodies. This approach has been used in humans to improve the effectiveness of plasmapheresis, another procedure that lowers serum level of antibodies. Similarly, this approach should also improve the effectiveness of IVIG.
[box type="orange"]Antibody: A protein produced by a B cell in response to a specific foreign substance. Antibodies are the ?soldiers? which protect us against bacteria and viruses and infections.

Cytotoxic drugs: Affect the growth and action of some cells that cause the joint pain, swelling, warmth, and damage of arthritis. Cytotoxic drugs work over a long period of time, however, patients may not notice much effect for the first several weeks or months of treatment.

Immunoglobulins: See Antibody

Plasmapheresis: Removal, tratamiento, and return of blood plasma from blood circulation.

* more definitions available here: www.pemphigus.org/glossary[/box]

Publicado en: Ensayos clínicos, Tema 54 - Otoño 2008
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