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The Journal of Immunology, 2005, 175: 7669-7677.
Copyright © 2005 by The American Association of Immunologists

Evidence for Multiple Shared Antigenic Determinants within Ro60 and Other Lupus-Related Ribonucleoprotein Autoantigens in Human Autoimmune Responses1

Rahul Pal2,*, Umesh S. Deshmukh*, Yukiko Ohyama3,*, Qiang Fang*, Carol C. Kannapell*, Felicia Gaskin{dagger} and Shu Man Fu4,*,{ddagger}

The Specialized Center of Research on Systemic Lupus Erythematosus, * Division of Rheumatology and Immunology, Department of Internal Medicine, {dagger} Department of Psychiatric Medicine, and {ddagger} Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908

Ab responses directed against several ribonucleoprotein (RNP) Ags are a characteristic feature of systemic lupus erythematosus (SLE). Previous work in our laboratory using mouse model systems had revealed that both epitope spreading and inherent cross-reactivity between ribonucleoproteins contributes to the observed multiple specificities in autoimmune sera. We have now extended these studies to human autoimmune responses. Using purified polyclonal and mAbs derived from SLE patients, cross-reactivity between Ro60 and SmD was demonstrated. The cross-reactive epitope was mapped to nonhomologous regions on Ro60481–505 and SmD88–102. Five mAbs specifically recognized apoptotic cells, demonstrated variable levels of cross-reactivity toward other nonhomologous ribonucleoprotein targets and bound multiple, nonoverlapping and nonhomologous epitopes on Ro60. Our study demonstrates that cross-reactivity between frequently targeted autoantigens is an important aspect of human systemic autoimmune responses. The presence of multiple cross-reactive epitopes on Ro60 might be important for the generation of anti-Ro60 Ab in SLE patients and in normal individuals displaying no evidence of clinical disease.


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The JI 2005 175: 7065-7066. [Full Text]  





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