Cartilage Attracts Immune Attack

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Cartilage Attracts Immune Attack

April 12, 2002

(Nature) -- Innocent proteins sucked up by cartilage may target

arthritis to joints, researchers say. The tissues attacked during

autoimmune disease may partly determine their own demise.

In the joint disease rheumatoid arthritis (RA), some patients

develop antibodies against common proteins found throughout the body.

Why only joints are affected is therefore a paradox.

One such protein is carried in the blood and settles on cartilage

tissue in joints, two U.S. teams have found, from studies in mice.

Antibodies bind the protein, called glucose-6-phosphate isomerase (GPI),

and trigger inflammation, they suggest. Thus, floating molecules that

attach to cartilage may localize the disease, they propose.

" I think the finding is important, " says immune system researcher

Toshio Hirano of Osaka University in Japan. The idea that local

properties of a tissue may help focus the disease could apply to other

autoimmune conditions, he suggests. However, this mechanism is unlikely

to underlie all cases of RA, which is thought to have many causes.

ROAD TO SELF DESTRUCTION

During rheumatoid arthritis, the delicate membrane lining the

joints fills with immune cells, causing inflammation and destruction of

the tissues. The disease affects 1-2 percent of people in the developed

world, yet the mechanism remains controversial and its trigger unknown.

Some researchers believe that the body produces autoantibodies

against proteins in joints. GPI could be one such; over half of RA

patients carry antibodies against their own GPI. Many others may be

involved.

Why the body develops such antibodies in the first place is

unresolved; genetic and environmental factors, such as infections, are

suspected.

" It's still wide open, " says of Washington University

School of Medicine in St. Louis, Missouri, who led part of the latest

research.

Other researchers doubt antibodies are involved at all: they think

that the immune system's T cells or blood cells cause the inflammation.

Nevertheless all agree that why the disease is specific to joints is an

important question.

" We don't understand exactly what is special about them, " says RA

specialist Marc Feldmann of Imperial College London.

JOINT APPROACH

GPI is inside all cells. It is normally involved in breaking down

sugars. Christophe Benoist of Harvard Medical School in Boston, Mass.,

and his team found that arthritic mice accumulated high levels of GPI on

the outside of cartilage cells in their joints.

and his team injected mice with radioactive antibodies that

recognize and stick to GPI. They tracked it using a mouse-sized version

of positron emission tomography (PET), a technique often used to scan

human brains.

" You can watch in real time where the antibody goes, " says.

Within 7 minutes it homed in on joints, they found.

It is unclear whether blocking this homing in would help to

prevent the human disease. Treating the downstream effects would be

easier, thinks . However, the PET method might be used to catch and

track the subtle early stages of the disease, he suggests, so that

treatment could be given sooner.

Many researchers remain unconvinced that animal models, of which

there are many, truly mimic the human disease.

" They could be red herrings, " warns RA researcher

of University College London.

Copyright 2002 Nature News Service. All rights reserved.