Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies

Anita P. Kuan, Winston Chamberlain, Susan Malkiel, Hsiao D. Lieu, Stephen M. Factor, Betty Diamond, Brian L. Kotzin

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Autoimmune disease involves both the development of autoreactivity and the expression of organ damage, and susceptibility is genetically complex. We recently reported that in autoimmune myocarditis susceptibility to antibody-mediated cardiac injury is strain specific. DBA/2 mice develop myocarditis following administration of myosin-specific antibody, while BALB/c mice do not. This susceptibility appears to be controlled by expression of myosin in the myocardial extracellular matrix. CByD2F1 mice are both resistant to induction of myocarditis and do not demonstrate extracellular myosin, indicating a recessive genetic component to these traits. A backcross analysis of susceptibility using DBA/2 x CByD2F1 mice revealed a locus on chromosome 12 that is strongly linked with myocarditis. In male mice there was a second region on chromosome 1 that also contributes to disease susceptibility. However, genetic susceptibility in both female and male mice was genetically complex. This study demonstrates that the genetic basis of tissue injury can be analyzed separately from the genetic basis of autoreactivity. Future studies will determine whether the genetic factors identified in this study are also involved in susceptibility to rheumatic fever.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalImmunogenetics
Volume49
Issue number2
DOIs
StatePublished - Jan 25 1999

Keywords

  • Antibody-mediated disease
  • Chromosome 12
  • Extracellular matrix
  • Myocarditis
  • Susceptibility genes

ASJC Scopus subject areas

  • Immunology
  • Genetics

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  • Cite this

    Kuan, A. P., Chamberlain, W., Malkiel, S., Lieu, H. D., Factor, S. M., Diamond, B., & Kotzin, B. L. (1999). Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies. Immunogenetics, 49(2), 79-85. https://doi.org/10.1007/s002510050466