The influence of variable-region somatic mutations on the specificity and pathogenicity of murine monoclonal anti-DNA antibodies.

Published

Journal Article

Antibodies to DNA (anti-DNA) occur prominently in systemic lupus erythematosus and provoke inflammatory damage in the kidneys. To determine the factors that confer pathogenicity on antibodies of this specificity, we investigated the in vitro and in vivo glomerular binding by members of four clonally related sets of monoclonal anti-DNA antibodies from lupus mice. Somatic mutations within the clonal sets enhanced binding to double-stranded DNA (dsDNA). Binding to permeabilized glomeruli in vitro was observed among affinity-purified preparations of these antibodies independent of specificity for dsDNA. In normal mice injected with hybridoma cell lines, nephritis as assessed by histology and immunofluorescence did not correlate with antibody affinity for DNA. By multivariate analysis, in vitro glomerular binding was the most predictive parameter of histologic outcome. These findings indicate that somatic mutations occurring during maturation of the autoimmune response do not necessarily enhance pathogenicity.

Full Text

Duke Authors

Cited Authors

  • Gilkeson, GS; Bernstein, K; Pippen, AM; Clarke, SH; Marion, T; Pisetsky, DS; Ruiz, P; Lefkowith, JB

Published Date

  • July 1995

Published In

Volume / Issue

  • 76 / 1 Pt 1

Start / End Page

  • 59 - 67

PubMed ID

  • 7606869

Pubmed Central ID

  • 7606869

International Standard Serial Number (ISSN)

  • 0090-1229

Digital Object Identifier (DOI)

  • 10.1006/clin.1995.1088

Language

  • eng

Conference Location

  • United States