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Murine genotype influences the specificity, magnitude and persistence of murine mercury-induced autoimmunity

Academic Article
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Overview

authors

  • Hultman, P.
  • Turley, S. J.
  • Enestrom, S.
  • Lindh, U.
  • Pollard, Kenneth Michael

publication date

  • April 1996

journal

  • Journal of Autoimmunity  Journal

abstract

  • Genetic factors are major contributors in determining the susceptibility to systemic autoimmune diseases. We studied the influence of genotype on systemic autoimmunity by treating female mice of the H-2s strains SJL/N, SJL/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody and tissue immune deposits during the subsequent 12 months. All strains developed antinucleolar antibodies (ANoA) of the IgG class which reacted in immunoblotting with a 34-kDa nucleolar protein identified as fibrillarin. The titre of ANoA attained after 10 weeks' treatment varied from 1:1,280 to 1:20,480 in the order: A.SW > SJL > > B10.S. Following cessation of HgCl2 treatment ANoA and antifibrillarin antibodies (AFA) persisted for up to 12 months, although some B10.S mice showed pronounced reduction not only of their autoantibody titres, but also systemic immune deposits when compared to other H-2s strains. A second set of autoantibodies targeted chromatin and in some mice specifically histones, and were distinguished from the ANoA by a rapid decline after treatment and a susceptibility linked to the non-H-2 genes of the SJL. Tissue levels of mercury remained elevated above untreated controls throughout the study period, suggesting that the mercury detected in lymphoid tissues may provide stimulation of lymphoid cells specific for fibrillarin for a considerable period after exposure has ceased. We conclude that H-2 as well as non-H-2 genetic factors distinctly influence not only the susceptibility to induction of autoimmunity, but also the specificity and magnitude of the response.

subject areas

  • Animals
  • Antibodies, Antinuclear
  • Antibody Specificity
  • Antigen-Antibody Complex
  • Autoimmune Diseases
  • Chromosomal Proteins, Non-Histone
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Genotype
  • H-2 Antigens
  • Immunoblotting
  • Kidney
  • Mercuric Chloride
  • Mice
  • Ribonucleoproteins
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Research

keywords

  • autoimmunity
  • genotype
  • immune-complex deposits
  • mercury
  • mice
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Identity

International Standard Serial Number (ISSN)

  • 0896-8411

Digital Object Identifier (DOI)

  • 10.1006/jaut.1996.0017

PubMed ID

  • 8738957
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Additional Document Info

start page

  • 139

end page

  • 149

volume

  • 9

issue

  • 2

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