Is α-Actinin A Target for Pathogenic Anti-DNA Antibodies in Lupus Nephritis?

Lesley J. Mason, Chelliah T. Ravirajan, Anisur Rahman, Chaim Putterman, David A. Isenberg

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Objective. Following recent reports that pathogenic murine anti-DNA antibodies bind to α-actinin, it was obviously of interest to assess the ability of human pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies to bind this antigen. Both human monoclonal anti-DNA antibodies and antibodies affinity purified from the sera of patients with systemic lupus erythematosus (SLE) were investigated. Methods. An enzyme-linked immunosorbent assay was established to measure immunoglobulin binding to α-actinin. Antibodies binding dsDNA were purified from the sera of SLE patients who either had active renal disease or had never had renal disease. Serum samples were selected at times when the patients' sera exhibited high IgG binding to dsDNA. The binding of supernatants from 3 high-affinity human anti-dsDNA IgG hybridomas (RH14, B3, and DIL-6) and 7 human IgM anti-DNA hybridomas was also investigated. Results. A greater proportion of anti-dsDNA IgG-binding antibodies purified from patients with renal disease bound to α-actinin than did those purified from the sera of patients without renal disease. The specificity of binding to the 100-kd α-actinin molecule was confirmed by Western blotting. The pathogenic human antibodies RH14 and B3 bound strongly to α-actinin, while nonpathogenic DIL-6 bound very weaky. RT84, the IgM antibody that binds dsDNA with the highest affinity, exhibited the greatest binding to α-actinin. Conclusion. The results of our study support the findings of previous studies using murine anti-DNA monoclonal antibodies, which suggest that pathogenic anti-dsDNA antibodies cross-react with α-actinin.

Original languageEnglish (US)
Pages (from-to)866-870
Number of pages5
JournalArthritis and Rheumatism
Volume50
Issue number3
DOIs
StatePublished - Mar 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Mason, L. J., Ravirajan, C. T., Rahman, A., Putterman, C., & Isenberg, D. A. (2004). Is α-Actinin A Target for Pathogenic Anti-DNA Antibodies in Lupus Nephritis? Arthritis and Rheumatism, 50(3), 866-870. https://doi.org/10.1002/art.20103