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A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production

Arthritis Research & Therapy Sep 09, 2017

Nakajima T, et al. – The researchers explored the expression cytokines in patients with Takayasu arteritis (TAK), stratifying them into those with or without the risk allele at the rs6871626 single nucleotide polymorphism (SNP). They suggested that the rs6871626 SNP in IL12B might influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines probably play a role in the pathophysiology of TAK.

Methods

  • With enzyme-linked immunosorbent assays, plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (Hcs).
  • Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified.
  • By flow cytometric analysis of peripheral blood mononuclear cells, the ratio of IFN-γ+ or IL-17A+ cells to CD4+T cells was measured.

Results

  • In patients with TAK, the levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher than in HCs, whereas there were no significant differences in the levels of plasma IL-23, supernatant IL-23, or supernatant IL-12p40.
  • The levels of plasma IL-12p70, supernatant IL-12p40, and supernatant IL-12p70 were significantly higher in patients with the risk allele than in those without.
  • In patients with the risk allele, the ratio of CD4+IFN-γ+ cells was significantly higher.
  • Whereas CD4+IL-17A+ cells displayed no differences.

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