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Cia25 On rat chromosome 12 regulates severity of autoimmune arthritis induced with pristane and collagen.
  1. Max Brenner
  1. Feinstein Institute for Medical Research, United States
    1. Teresina Laragione
    1. Feinstein Institute for Medical Research, United States
      1. Adriana Mello
      1. Feinstein Institute for Medical Research, United States
        1. Pércio S. Gulko (pgulko{at}nshs.edu)
        1. Feinstein Institute for Medical Research, United States

          Abstract

          Background: A genome-wide scan in a DAxACI F2 intercross studied for collagen-induced arthritis (CIA) identified the severity quantitative trait locus Cia25 on rat chromosome 12. Cia25 co-localizes with loci regulating several forms of autoimmune diseases in rats, mice and humans, suggesting a common gene.

          Objective: To characterize the effects of Cia25 on arthritis severity in congenic rats.

          Methods: DA.ACI(Cia25) congenic rats were constructed according to a genotype-guided strategy, and tested for pristane-induced arthritis (PIA), and CIA induced with rat type II collagen (CII). A well- established scoring system previously shown to correlate with histologic damage, including cartilage and bone erosions, synovial hyperplasia, and synovial inflammation was used.

          Results: The introgression of ACI alleles at Cia25 into DA background, as in DA.ACI(Cia25) rats, was enough to significantly reduce arthritis severity by 60% in PIA, and 40% in CIA, both in males and females compared with same sex DA. Levels of IgG anti-CII in male DA.ACI(Cia25) rats were 83% lower than in male DA. Levels of anti-CII in females were not affected by the congenic interval.

          Conclusions: Cia25 contains a gene that regulates disease severity in two distinct models of autoimmune arthritis. While both genders were protected in arthritis studies, only male congenics had a dramatic reduction in levels of anti-CII, suggesting the possibility of a second arthritis gene in this interval that operates via the regulation of autoantibodies in a sex-specific manner. The identification of the gene(s) accounting for Cia25 is anticipated to generate novel prognostic biomarkers, and targets for therapy.

          • autoantibody
          • autoimmunity
          • genetic
          • rheumatoid Arthritis
          • rodent

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