Biomedicine

A Robust Revelation in Lupus

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Science  20 Jun 2003:
Vol. 300, Issue 5627, pp. 1851
DOI: 10.1126/science.300.5627.1851c

Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease that affects multiple organ systems and is characterized by a range of symptoms, including kidney disease, arthritis, cardiopulmonary abnormalities, and skin photosensitivity. Autoantibodies against cellular macromolecules such as chromatin, phospholipids, and ribosomes have been identified in SLE patients, suggesting that the formation of immune complexes may lead to tissue inflammation and damage.

Xue et al. report that mice lacking an RNA-binding protein called Ro (a known SLE autoantigen) develop antibodies against ribosomes and chromatin. These mice display glomerulonephritis and skin photosensitivity reminiscent of the human disease even though their immune systems appear normal. Previous work in the frog Xenopus and worm Caenorhabditis elegans revealed that Ro may be a component of a ribosomal quality-control pathway in which misfolded 5S ribosomal RNA (rRNA) molecules are degraded before they become incorporated into ribosomes. In addition, Ro helps the bacterium Deinococcus radiodurans to withstand ultraviolet irradiation and C. elegans to withstand environmental stress. These authors propose that loss of Ro in mice may lead to incorporation of misfolded 5S rRNAs into ribosomes, resulting in the presentation of hidden epitopes to the immune system, the formation of antibodies to ribosomes, and the development of autoimmune disease.—OMS

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.0832411100 (2003).

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