The findings suggest that abnormalities in a protein called Ro 60-kDa could cause the disease. The discovery also hints that the protein might normally play a protective role in the body by "hiding" defective complexes of RNA and protein, called ribonucleoproteins, from attack by the immune system.

The research team, which included Sandra Wolin and Richard Flavell, both HHMI investigators at Yale University School of Medicine, published its findings June 3, 2003, in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

According to Wolin, Ro has long been known to be an autoantigen in lupus patients. Autoantigens trigger the immune system to produce antibodies that attack the body's own components, resulting in autoimmune disease. Despite Ro's known role as an autoantigen, researchers have had a difficult time determining whether the autoantibodies directed against Ro and other autoantigens cause diseases like lupus. "Many rheumatologists think that the autoantibodies are an epiphenomenon -- an interesting phenomenon but not directly related to the cause of lupus," said Wolin.

The normal role of Ro was not well understood although it was known that the protein is normally found bound to small RNA molecules called Y RNAs, whose function remains somewhat mysterious. Wolin and her colleagues had begun to answer questions about Ro's function when their earlier experiments demonstrated that the Ro protein binds to small RNA molecules that are misfolded versions of those that help make up the cell's ribosomes, which are its protein assembly lines.

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
2-Jun-2003