Link between Salmonella and Arthritis
Research that was performed at Johns Hopkins and published in the February 2002 issue of Nature Medicine, revealed a connection between certain bacterial infections and autoimmune disease. If normal cells carry a specific protein that mimics the bacterial protein, they may be attacked by the immune system.
If there has been a bacterial infection, cells that have been infected by the bacteria display some of the bacteria’s protein. It is a way to signal the immune system that the cell is sick and needs to be dealt with. They have a protein marker that triggers the immune system into action.
However, immune cells can attack cells that bacteria have never infected and should be left alone. This especially occurs when the cells are stressed by exposure to irradiation, environmental toxins or the body’s stress chemicals. The scientists first identified the protein marker in mouse cells infected with Salmonella as one common to certain bacteria associated with human arthritis. But they also found that the bacterial marker was almost identical to parts of a molecule found in humans, mice and all living organisms.
In a normal Salmonella infection in mice, at least half of the immune cells are stirred up to recognize the mouse’s own protein as well as the bacterial one. When researchers artificially caused the mouse body cells to mimic the Salmonella protein, the mouse immune cells would readily attack them. The immune cells also went into attack mode if the cells displayed a piece of the mouse’s own molecule (the one similar to that of the bacteria) or the identical human version. In other words, the immune system can be triggered by a mimic, even if that mimic is part of the host’s own body. An autoimmune response is created.
Mark Soloski, Ph.D, who led the research team said that the amount of those who get Salmonella can be as high as 10%. He said that they develop a reactive kind of arthritis lasting a few weeks. He also said that a smaller, significant number of those patients get a severe, debilitating type of arthritis that is long-lasting.
That’s a huge immune response.” Based on the similarity of the set-up in humans, he adds, the response is likely the same. Now the scientists are trying to find why and how this immune response translates into arthritis in some mice and humans.
In a small side study, the team also found that normal, uninfected body cells could be attacked by CTLs if the cells were stressed in some way, such as being exposed to higher temperature or radiation or general infection. “We don’t know what’s going on here,” says Soloski, “but it’s a good place to study other triggers of autoimmune diseases.”
Other researchers were lead author Wei-Feng Lo, M.D., Ph.D., Amy DeCloux, Ph.D., Amina S. Woods, Ph.D., and Robert J. Cotter, Ph.D., of Hopkins, as well as Eleanor S. Metcalf, Ph.D., of the Uniformed Services University of the Health Sciences in Bethesda, Md.
The research was funded by NIH grants and by an award from the Maryland Chapter of The Arthritis Foundation.