The kinder side of the E.coli bug

February 4, 2000

The fight against auto-immune diseasecould get help from an unlikely source, says Geoff Watts

As the raw material for a new way of treating rheumatoid arthritis, the poison produced by a diarrhoea-inducing bacterium does not sound too promising. Neil Williams of Bristol University's department of immunology thinks otherwise.

The bacterium itself is a variety of E. coli, one of the commonest causes of diarrhoea. The watery outpouring serves the organism's purposes by ensuring that its descendants are spread far and wide, and so stand a fair chance of reaching the drinking water of some other potential host.

The poison with which E. coli engineers intestinal mayhem is a protein comprising two chunks referred to as the A and B sub-units. "The A sub-unit is the bit that actually gets into the cells of the gut and makes them secrete water and so cause diarrhoea," explains Dr Williams. "We're working on the B sub-unit. On its own it is not toxic. The bacteria use it just to get the A sub-unit into the gut cells. B sub-units do this by binding to receptors, specialised molecules on the surfaces of the cells."

Isolated B sub-units still bind to cell surface receptors, says Dr Williams. But with no toxic payload to deliver, that is all they do - at least to gut cells. "What we noticed a few years ago was that if they attach not to gut cells but to those within the immune defence system, they can actually modify the way these cells behave."

Rheumatoid arthritis is an auto-immune disease: one in which the immune defence system begins to attack part of the body it is supposed to be protecting. Evolution has produced an elaborate and effective method of distinguishing self from non-self and acting accordingly. But there is, inevitably, a balance to be struck. The exercise of vigilance sufficient to destroy all bacteria, viruses and other genuine intruders must be prevented from turning into a gung-ho assault on any bit of the body itself that raises the tiniest hint of suspicion.

"Auto-immune disease is a process in which that balance has gone wrong," says Dr Williams. "The immune system fails to recognise that, in the case of arthritis, components of our joints are actually part of us. It starts to see them as if they're foreign and need to be attacked."

Success in treating auto-immunity depends on being able to suppress those processes that are misbehaving while leaving the rest of the immune system to get on with its useful work. As Dr Williams and his colleagues began to study the actions of their protein sub-unit, they realised that the changes it can make to the immune system might well cause it to suppress the sort of damage that leads to arthritis. Animal models confirmed their hopes.

"What we are attempting to do to these cells is not destroy them but re-educate them. We've started work with human blood samples to see that the sort of effects we are looking for do also occur in humans. We are very hopeful that the data we already have make a strong case for a clinical trial."

The protein can be administered by injection, by mouth and even by nasal spray. And if it works in rheumatoid arthritis, Dr Williams is hopeful that it might also be effective in other auto-immune conditions such as multiple sclerosis.

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