Soluble receptor against lupus?

Shown: Kidney sections; G = glomeruli Credit: © ZymoGenetics

A soluble form of a receptor for a cytokine that activates B cells is effective for inhibiting the development of autoimmune disease in a mouse model of systemic lupus erythematosus (SLE), according to a study recently published in Nature (404, 995–999, 2000). The results validate a genomic screening approach for identifying protein ligands and may open a promising avenue to treating human autoimmune diseases. Researchers at ZymoGenetics (Seattle, WA) first showed that the cytokine (zTNF4), a member of the tumor necrosis factor (TNF) ligand family, causes SLE-like symptoms in mice when overexpressed. They then identified TACI, a receptor for zTNF4, by screening a cDNA expression library prepared from B cells with a labeled form of the cytokine. Reasoning that the TACI–zTNF4 interaction could be of potential therapeutic value, the researchers then set about creating a soluble form of TACI and tested it in the mouse SLE model. The treatment inhibited the development of proteinuria in the animals and prolonged their survival. Although the results are promising, the researchers acknowledge that more work must be done to determine the possible side effects of inhibiting B-cell activation with TACI. “We are currently testing the effects of TACI treatment on the development of a normal immune system and during a primary and secondary immune response,” says Jane Gross, a company scientist and lead author on the paper.

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Dove, A. Soluble receptor against lupus?. Nat Biotechnol 18, 585 (2000).

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