Garvan team spotlights role of rogue cells in autoimmune diseases

Garvan Professor Robert Brink

The human body naturally produces antibodies to ward off invaders like bacteria. But when the process goes awry, rogue antibodies are directed at the body itself, causing autoimmune diseases like rheumatoid arthritis. And now a group of researchers at Australia's Garvan Institute of Medical Research say they believe that they have identified at least part of what can go wrong, highlighting some potential targets for drug developers.

In a normal response to invaders, B cells are responsible for creating antibodies. But the investigators say that mutations in the FAS molecule create what they call "rogue germinal center B cells" that spur plasma cells to create autoimmune antibodies.

"In very simple terms, we believe FAS prevents rogue germinal center B cells from developing, and we suspect that is its primary role," said Garvan professor Robert Brink. "When we removed FAS from a mouse model, we saw the appearance of rogue cells in the germinal center, and the plasma cells they produced, and neither obeyed any of the normal rules. A disproportionately large number of plasma cells were formed by these rogue cells, producing antibodies you wouldn't expect to see, very high numbers of IgE antibodies in particular. Instead of getting better at binding foreign antigen, rogue cells got worse--the opposite of what is supposed to happen in the germinal centre! Most significantly, many of the antibodies derived from rogue cells turned out to be autoantibodies."

In autoimmune lymphoproliferative syndrome, they add, there's data that shows about a quarter of the patients involved have high levels of IgE, indicating that this mouse study is relevant to humans.

"High levels of IgE antibodies are being found in other autoimmune diseases, such as lupus, and IgE is becoming increasingly associated with severe disease," Brink added. And there are likely other mechanisms in the body that trigger these rogue cells, marking it as a key area for investigators to explore further.

- here's the release

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