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Lifescientist: Garvan team solve autoimmune mystery

Firestormm

Senior Member
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Location
Cornwall England
Garvan team solve autoimmune mystery

A team at the Garvan Institute has solved a longstanding mystery as to how some autoimmune diseases can be triggered by wayward B cells.
The immune system is startlingly complex and generally incredibly effective at warding of foreign invaders. But occasionally it turns on its own tissue, causing autoimmune diseases like rheumatic fever or Guillain-Barré syndrome.

Sometimes these autoimmune diseases are triggered by an outside infection, with the immune system mistakenly leaping into action against the wrong cells.

It’s like your computer security program deleting your essential files after it has removed a virus from the system.

Now a team at the Garvan Institute has uncovered the mechanism that can cause the immune system to backfire, solving a longstanding mystery of how these autoimmune diseases can be triggered by an external infection.

Our immune cells, such as the antibody-creating B cells, go through processes when they are first formed that ensure they are able to identify our own bodies, and therefore avoid self-attack. These processes are generally reliable as they take place in a steady, regulated way.

B cells go through a second and much more chaotic phase of development, however, when the body is fending off disease or infection. In order to cope with the immeasurable range of microbes in our environment, B cells have evolved the ability to mutate their antibody genes randomly until they produce one that sticks strongly to the invader. At that point, the ‘successful’ B cells proliferate and flood the system with these new antibodies.

This ‘high affinity antibody’ generation occurs very rapidly within specialised environments in the lymph system known as ‘germinal centres’. Most of the time, germinal centres serve us well, helping us fight disease and build up a protective armoury for the future.

However, the urgency and speed at which B cells mutate within the germinal centre, as well as the random nature of the process, creates a unique problem. Sometimes the antibody created to fight the invader, or ‘antigen’, also happens to match ‘self’ and has the potential to cause autoimmune attack.

Dr Tyani Chan and Associate Professor Robert Brink used mouse models to show this process in action, finding that when target antigen is located only in a tissue or organ remote from the germinal centre, B cells capable of reacting against both antigen and ‘self’ are able to escape the germinal centre and produce autoantibodies.

“Essentially we’ve shown there’s a big hole in self-tolerance when it comes to cross-reactive autoantibodies that can attack organ-specific targets,” said Brink.

“Our finding explains a lot about how autoimmune conditions that target particular organs such as the heart or nervous system could develop after an infection. It also suggests that if you know enough about the disease and the molecular messaging systems involved, it may be possible in future to modulate the germinal centre response.”

The team will continue to use their new mouse model to study the various molecular reactions involved in the progression of an autoimmune response.

The paper was published today in Immunity.

Early days then. They're still milking the mice :) Still, could this kind of think have ought to do with that Rituximab stuff? Who knows?! But the notion that an infection could trigger an autoimmune condition in such a way, is fascinating. Go science. Now all we need is for this to be confirmed as happening in HUMAN BEINGS....