Evidence for multiple shared antigenic determinants within Ro60 and other lupus-related ribonucleoprotein autoantigens in human autoimmune responses

Rahul Pal, Umesh S. Deshmukh, Yukiko Ohyama, Qiang Fang, Carol C. Kannapell, Felicia Gaskin, Shu Man Fu

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7669-7677
Number of pages9
JournalJournal of Immunology
Volume175
Issue number11
DOIs
Publication statusPublished - Dec 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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