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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
Nakajima Toshiki
Yoshifuji Hajime
Shimizu Masakazu
Kitagori Koji
Murakami Kosaku
Nakashima Ran
Imura Yoshitaka
Tanaka Masao
Ohmura Koichiro
Matsuda Fumihiko
Terao Chikashi
Mimori Tsuneyo
Arthritis Research and Therapy, 19(1), pp 197, 2017-9-6
Summary
Background: A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of these cytokines in patients with TAK, stratifying them into those with or without the risk allele at the rs6871626 SNP. Methods: Plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (HCs) by enzyme-linked immunosorbent assays. Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-gamma (IFN-gamma) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-gamma(+) or IL-17A(+) cells to CD4(+) T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells. Results: The levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher in patients with TAK 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. The ratio of CD4(+) IFN-gamma(+) cells was significantly higher in patients with the risk allele, whereas CD4(+) IL-17A(+) cells showed no differences. Conclusions: The rs6871626 SNP in IL12B may influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines might play roles in the pathophysiology of TAK.
Keywords
Takayasu arteritis; Vasculitis; Interleukin-12; Single nucleotide polymorphism; Monocytes
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