Ro's role in lupus

An estimated 1.5 million Americans suffer from lupus erythematosus, an autoimmune disorder that causes aching joints, fever, fatigue, numerous skin lesions and hypersensitivity to light. Many lupus patients carry in their blood an antibody against the autoantigen Ro 60-kDa. This RNA-binding protein passes unnoticed in the normal immune system but is the target of an abnormal immune response in these patients. Nevertheless, the role of Ro in lupus erythematosus has been unclear.

When Sandra L. Wolin, M.D./Ph.D. ’85, associate professor of cell biology and molecular biophysics and biochemistry and a Howard Hughes Medical Institute associate investigator, and colleagues developed a knockout mouse without the gene for making the Ro protein, the mouse developed an autoimmune syndrome similar to lupus. The authors suggest that Ro may serve a quality control function by recognizing misfolded, defective RNA molecules. When Ro is absent, abnormal RNA-protein complexes may accumulate and be viewed as foreign by the immune system.