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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

Authors
  • Nakajima, Toshiki1
  • Yoshifuji, Hajime1
  • Shimizu, Masakazu2
  • Kitagori, Koji1
  • Murakami, Kosaku1
  • Nakashima, Ran1
  • Imura, Yoshitaka1
  • Tanaka, Masao3
  • Ohmura, Koichiro1
  • Matsuda, Fumihiko2
  • Terao, Chikashi2
  • Mimori, Tsuneyo1
  • 1 Kyoto University, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan , Kyoto (Japan)
  • 2 Kyoto University, Center for Genomic Medicine, Graduate School of Medicine, Kyoto, Japan , Kyoto (Japan)
  • 3 Kyoto University, Department of the Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto, Japan , Kyoto (Japan)
Type
Published Article
Journal
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Publication Date
Sep 06, 2017
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s13075-017-1408-8
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundA 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.MethodsPlasma 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-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-γ+ or IL-17A+ cells to CD4+ T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells.ResultsThe 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-γ+ cells was significantly higher in patients with the risk allele, whereas CD4+IL-17A+ cells showed no differences.ConclusionsThe 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.

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