The role of somatic mutation in the pathogenic anti-DNA response

Betty Diamond, Jessica B. Katz, Elahna Paul, Cynthia Aranow, Daniel Lustgarten, Matthew D. Scharff

Research output: Contribution to journalReview articlepeer-review

234 Scopus citations


Anti-DNA antibodies represent a significant autospecificity in systemic lupus erythematosus because they are essentially diagnostic of the disease and they contribute to renal pathology. The molecular genetic characterization of these antibodies from both lupus-prone mice and humans with lupus has shown them to be somatically mutated. In many cases the nature of the mutations suggests that DNA or some structurally homologous molecule is driving the response. In other cases the high replacement-to-silent mutation ratio in framework regions of the antibody suggests selection by idiotype or by some mechanism other than antigen itself. Current studies of immunoglobulin variable region genes encoding antiDNA antibodies reveal no disease associated polymorphisms. There are also no data suggesting that the nature of the recombination process that forms intact variable region genes or of the process of somatic mutation differs in autoimmune and nonautoimmune strains or kindred. Current data suggest, rather, that a defect in regulation is responsible for autoantibody production in SLE. The finding that most if not all anti-double stranded DNA antibodies are somatically mutated suggests the defect is in maintenance of peripheral rather than central tolerance.

Original languageEnglish (US)
Pages (from-to)731-757
Number of pages27
JournalAnnual Review of Immunology
StatePublished - 1992


  • B-cell geneologies
  • autoantibody regulation
  • idiotype
  • variable region genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'The role of somatic mutation in the pathogenic anti-DNA response'. Together they form a unique fingerprint.

Cite this