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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

Development of B-Cell Superantigen-Based Therapy in SLE: Phase II

Silverman, Gregg, MD

University of California, San Diego

In the first phase of this project, Dr. Silverman showed that a protein made by staphylococcus aureus (staph) bacteria acts as a selective B-cell toxin in mice, killing targeted B cells without harming other cells in the body. Preliminary studies also indicated that this bacterial protein, called staphylococcal protein A (SpA), could selectively target and eliminate B cells in non-human primates. B cells are white blood cells that normally help the immune system fight infections. They also play a central role in the development of lupus, producing antibodies that attack the body’s own tissues. In the second phase of this project, Dr. Silverman will study the detailed mechanisms by which SpA causes targeted B-cell death and examine whether SpA and rituximab act through common pathways to trigger the death of B cells. Rituximab is a genetically engineered antibody that also targets and kills B cells and is being examined as a potential therapy for lupus. However, researchers do not have a clear understanding of how rituximab works.

What this study means for people with lupus: Current therapies for lupus act mainly by suppressing the immune system, and they often result in increased susceptibility to infection or other adverse side effects. Because SpA attacks only certain B cells in the immune system in primates as well as mice, it might be used to selectively eliminate those B cells involved in lupus, leaving infection-fighting B cells unharmed. In addition, Dr. Silverman’s studies comparing how SpA and rituximab work to selectively target and kill B cells should provide insights that will help develop safe and practical new approaches for treating SLE.


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