Pathogenic anti-DNA antibodies in SLE: Idiotypic families and genetic origins

Elahna Paul*, Audrey Manheimer-Lory, Avi Livneh, Andrew Solomon, Cynthia Aranow, Cybele Ghossein, Rachel Shefner, Daniel Offen, Michael Pillinger, Betty Diamond

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 31, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 31 autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)295-313
Number of pages19
JournalInternational Reviews of Immunology
Volume5
Issue number3-4
DOIs
StatePublished - 1990

Keywords

  • Anti-DNA antibodies
  • Idiotypes
  • SLE
  • Somatic mutation
  • Variable region genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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