Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies

Sandra Sciascia, Kristina Robson, Liangjin Zhu, Michael Garland, Shannon Grabosch, Joseph Kelamis, Will Messamore, Todd Bradley, Allison Sourk, Lindsey Westberg, Waco Goodnight, Krystina Tongson, Naomi Holloway, Zabi Wardak, Michelle Sudyka, Shriti Masrani, Sanket Chintalapati, Manuel Cagaanan, J. C. Brown John, Dean A. Stetler

Research output: Contribution to journalArticlepeer-review

Abstract

Antibodies against the N-terminal (NT) but not the basic domain (BD), DNA binding regions of the largest subunit (S1) of RNA polymerase I (RNAPI) were detected in the sera of MRL-lpr/lpr lupus mice. Antibodies against both RNAPI(S1)-NT and -BD, as well as other systemic lupus erythematosus (SLE) autoantigens (La, ribosomal P proteins and Sm/RNP) were produced by rabbits immunized with anti-DNA antibodies that had been affinity purified from SLE patients. Immunization of nonautoimmune mice (Balb/c) with RNAPI(S1)-NT, RNAPI(S1)-BD, or La in the form of GST fusion proteins, induced production of anti-double-stranded (ds) DNA and anti-Sm/RNP. GST-P1 did not induce an anti-dsDNA response in these mice. These results demonstrate that RNAPI(S1)-NT, RNAPI(S1)-BD and La can participate in an anti-autoantigen/anti-DNA antibody loop during an SLE-like autoimmune response.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalAutoimmunity
Volume40
Issue number1
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • Anti-70.kDa U1-RNP antibodies
  • Anti-dsDNA antibodies
  • Lupus
  • RNA polymerase I
  • SLE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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