Initiation of systemic autoimmunity and sequence specific anti-DNA autoantibodies.

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  • Author(s): Radic MZ;Radic MZ; Cocca BA; Seal SN
  • Source:
    Critical reviews in immunology [Crit Rev Immunol] 1999; Vol. 19 (2), pp. 117-26.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Begell House Country of Publication: United States NLM ID: 8914819 Publication Model: Print Cited Medium: Print ISSN: 1040-8401 (Print) Linking ISSN: 10408401 NLM ISO Abbreviation: Crit Rev Immunol Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Begell House
      Original Publication: Boca Raton, Fla. : CRC Press, c1980-
    • Subject Terms:
      Antibody Specificity*; Amino Acid Sequence/*immunology ; Antibodies, Antinuclear/*biosynthesis ; DNA/*immunology ; Lupus Erythematosus, Systemic/*immunology; Animals ; Autoantigens/immunology ; Humans ; Lupus Erythematosus, Systemic/etiology
    • Abstract:
      Antibodies to double-stranded DNA (dsDNA) are a defining feature of Systemic Lupus Erythematosus (SLE). The molecular characterization of anti-dsDNA autoantibodies reveals that they are actively selected for binding to antigen. Evidence for antigen selection includes the use of suitable rearrangement products, the switching of IgM isotype to IgG, and the acquisition of somatic mutations that raise the affinity for dsDNA. Through a process of specificity maturation, anti-dsDNA antibodies can arise from anti-single stranded DNA (ssDNA) antibodies that also occur in nonautoimmune individuals. To clarify circumstances leading to the initiation of systemic autoimmunity, we compare features of immune responses to nucleic acids that operate before and after disease develops. Evidence indicating that anti-dsDNA antibodies bind with DNA sequence preference is highlighted to propose that sequence-specific anti-dsDNA antibodies may be induced by an infectious agent and in turn may extend the response to endogenous nuclear antigens. Thus, sequence-specific anti-dsDNA B cells may provide an important stimulus to break the tolerance to self.
    • Number of References:
      76
    • Grant Information:
      AI-34881 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Antibodies, Antinuclear)
      0 (Autoantigens)
      9007-49-2 (DNA)
    • Publication Date:
      Date Created: 19990603 Date Completed: 19990712 Latest Revision: 20071114
    • Publication Date:
      20221213
    • Accession Number:
      10352900