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Autoimmune Dis. 2014;2014:260613. doi: 10.1155/2014/260613. Epub 2014 Apr 10.

A tandem repeat in decay accelerating factor 1 is associated with severity of murine mercury-induced autoimmunity.

Author information

1
Department of Surgery, University of California, San Diego, 9500 Gilman Drive, No. 0739, La Jolla, CA 92093-0739, USA.
2
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Molecular and Immunological Pathology, Department of Experimental and Clinical Medicine, Linköping University, 581 83 Linköping, Sweden.

Abstract

Decay accelerating factor (DAF), a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA). Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

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