Researchers investigating the method that Staphylococcus aureus (“staph”) bacteria use to disable the body’s immune response during an infection have provided insights that may lead to new, more targeted therapies to eliminate harmful B cells in people with systemic lupus erythematosus (SLE, or lupus). B cells, or B lymphocytes, are white blood cells that normally help the immune system fight infections. They also play a central role in the development of SLE, in which the immune system turns against the body’s own tissues.
In studies with mice, Alliance for Lupus Research (ALR) investigator Gregg Silverman, MD, and Carl Goodyear, PhD, of the University of California, San Diego, demonstrated that a protein made by the staph bacteria acts as a selective B-cell toxin. The staph protein, called SpA, attacks B cells in a manner that Dr. Silverman describes as a “‘smart bomb’ approach” because it kills the targeted cells without harming other cells in the body. The results of these studies—supported in part by the ALR—were published in the May 5, 2003 issue of the Journal of Experimental Medicine.
In recent preliminary experiments funded by ALR, Dr. Silverman found that B cells in non-human primates are also susceptible to killing by SpA. This finding “strongly indicates the potential for using this protein in human therapy,” Dr. Silverman says. “It’s not just mice that are susceptible.”
What it means for people with lupus: “These findings will allow us to proceed to the next step, to test the protein’s usefulness in people,” says ALR Scientific Director John H. Klippel, MD. “If the results hold true for people, SpA may eventually prove to be an effective treatment for lupus.” Because SpA attacks only certain B cells in the immune system, the researchers hope it can be used to selectively eliminate B cells involved in lupus. “We are in the process of adapting SpA so we can pick and choose which B lymphocytes are targeted, so it won’t wipe out all of them,” Dr. Silverman says. This would be a significant advantage over many current lupus treatments, which harm healthy cells including infection-fighting B cells and thus can have serious side effects. Dr. Silverman notes that these studies have also provided new insights into the mechanisms by which B cells can be targeted for death, which may suggest other therapeutic approaches directed at B cells.
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