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Gene Mutation That Causes Problems To Vaccines Identified

by Aruna on  November 12, 2009 at 8:48 AM Research News   - G J E 4
Gene Mutation That Causes Problems To Vaccines Identified
Reports say that a mutation in the gene, called Dock8, could make the body 'forget' it has ever been vaccinated, a discovery that could lead to better vaccinations.
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Clinical immunologist Dr Katrina Randall of The Canberra Hospital has said that the findings could improve treatment of transplant rejection, autoimmunity and allergy.

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She said that there are some people who have problems making a proper response to vaccines, and to understand this, the researchers conducted their studies on genetically mutated mice models.

"We were investigating these mice and we found they had a very good response to their first vaccination and were making antibodies," ABC Science quoted her as saying.

But on re-examination after a week, no antibodies were found in the mice, said Randall.

She said that because the genetic mutations in the mouse models were random, they had to search for the specific gene responsible for the malfunctioning antibodies.

After carrying out association studies to find the precise genetic region involved, the team found that a mutation in the gene Dock8 was causing the problem.

"We then wanted to look at the functional consequences of the mutation," said Randall.

She says in normal mice the vaccine would interact with specialized white blood cells called B cells to create antibodies and over time, these antibodies built up to form a protective army in case the mice ever be infected by the target pathogen.

"Immunity normally lasts for years after we are immunized or infected because our immune system remembers the shape and 'fingerprints' of an infecting microbe and keeps making antibodies against them," she added.

Randall says the interaction between the B cells and the antigen [vaccine] occurs at the B cell synapse, but a mutation in the Dock8 gene stops this interaction from taking place.

Randall and her team believe without this interaction the B cells die before they've had a chance to become long lived memory B cells.

"If the synapse isn't formed properly then the cells die out before they've had a chance to make the long lived antibodies and before they've been able to make the memory B cells, that circulate to give you long term immunity," she said.

Randall says this work could lead to better treatment of people whose bodies are unable to produce an immune response to vaccinations. It could also help scientists develop better vaccines.

The study has been published in the latest edition of Nature Immunology.

Source: ANI
ARU
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