Vaccine against autoimmune diseases

Scientists have tested vaccination against autoimmune diseasesLeonid Popov, Membrane
Biologists from the Weizmann Institute forced the immune system of animals to fight the disease associated with errors in the work of this system itself.

For the virtuoso deception of the body, the authors used synthetic substances that imitate natural ones.

A group led by Professor Irit Sagi learned to control the activity of matrix metalloproteinases (MMP) in the body.

This group of enzymes plays an important role in wound healing, tissue restructuring, cell migration and mobilization, the creation of new blood vessels, cell differentiation and apoptosis. But in case of malfunction, these same proteins contribute to the development of autoimmune diseases, as well as malignant tumors, explains EurekAlert (New synthetic molecules treat autoimmune disease in mice).

Initially, the researchers tried to design substances aimed against the MMP themselves, but it turned out that such drugs are too crude weapons with severe side effects. Meanwhile, the body has a natural control mechanism – endogenous metalloproteinase inhibitors (TIMP). Alas, it turned out to be impossible to reproduce these very complex compounds artificially.

That's when the experimenters came up with a deceptive move: they decided to train the immune system of experimental animals to strengthen the suppression of MMP.

Each such enzyme has an active site – a zinc ion surrounded by three histidine peptides. It is this fragment of MMP that recognizes and blocks the TIMP inhibitor.

Zinc-histidine complex (right)
lies at the heart of the MMP enzyme (left)
and is a lock for the inhibitor key
(illustration by Netta Sela-Passwell, Irit Sagi et al./ Nature Medicine).

The Israelis created an artificial version of the zinc-histidine complex, taking as a basis the structure of a specific MMP9 metalloproteinase. (The diagram from the same article shows the formula and structure of an artificial molecule used for a kind of immunization.)

When scientists injected these small molecules into mice, the animals developed an immune response to MMP. New antibodies were found in the blood of rodents. They did not copy exactly, but were very similar in structure to TIMP connections.

Biologists dubbed newcomers metallotelami. Analysis of the structure of these molecules showed that they should work similarly to TIMP – block the active center of an undesirable enzyme.

Further, it turned out that the metalloteles produced by animals acted very selectively – only against MMP9 and MMP2. And this is just in the hands of potential therapy, whose task is to reduce the activity of strictly defined enzymes.

Left: A natural inhibitor (gray) is attached to the active center (yellow) of the MMP molecule (red).
On the right: a new antibody successfully performs the same task (illustration by Weizmann Institute of Science).

To finally test the idea, the authors of the work caused an inflammatory disease in mice that mimics Crohn's disease (it is believed that it has an autoimmune nature). The animals that were immunized with synthetic molecules did not show symptoms of the disease.

So biologists have shown that molecular mimicry encourages the body to adjust its immune system to fight an enzyme, an excess of which leads to autoimmune ailments.

Details of the study can be found in an article in Nature Medicine (Sela-Passwell et al., Antibodies targeting the catalytic zinc complex of activated matrix metalloproteinases show therapeutic potential).

Portal "Eternal youth" http://vechnayamolodost.ru
27.12.2011