Article Text

PDF
OP0056 Association of IL-12P40 and IL-12P70 with Pathophysiology of Takayasu Arteritis
  1. T. Nakajima1,
  2. H. Yoshifuji1,
  3. C. Terao2,
  4. K. Kitagori1,
  5. K. Murakami1,
  6. R. Nakashima1,
  7. Y. Imura1,
  8. M. Tanaka1,
  9. K. Ohmura1,
  10. T. Mimori1
  1. 1Department of Rheumatology and Clinical Immunology Graduate School of Medicine, Kyoto University
  2. 2Center for Genomic Medicine. Kyoto-University, Kyoto, Japan

Abstract

Background We preliminarily found a SNP (rs6871626, A vs. C) in IL-12B region as a susceptibility gene to Takayasu arteritis (TAK) by genome-wide association study. IL-12B encodes IL-12p40 that is a component of both IL-12p70 and IL-23. The significance of IL-12p40 in pathophysiology of TAK has not been fully investigated yet. Moreover, there has been no consistent evidence about whether IL-12p70 or IL-23 is important in TAK.

Objectives 1) To investigate the expression of IL-12p40 in patients with TAK, 2) reveal which is more important to pathophysiology of TAK, IL-12p70 or IL-23, and 3) examine the influence of SNP to the cytokine production.

Methods We collected sera from 43 TAK patients and 19 healthy controls (HCs), and measured IL-12p40, IL-12p70 and IL-23 with ELISA. Next, we collected whole blood from 18 TAK patients and 12 HCs, and isolated monocytes with RosetteSep™. The monocytes were incubated with IL-6, IL-10 and GM-CSF, and then stimulated with INF-γ and LPS. Then we measured the cytokines in culture supernatant with ELISA.

Results IL-12p40 and IL-12p70 in sera of TAK patients were significantly higher than those of HCs (p=0.031 and p<0.001, respectively), whereas there were no differences in serum of IL-23 levels between TAK patients and HCs. IL-12p40 and IL-12p70 in sera of TAK patients whose allele at rs6871626 is AA or AC (defined as risk patients) were significantly higher than those of HCs (p=0.018 and p<0.001, respectively), whereas there were no differences in serum IL-23 levels among risk patients, TAK patients with CC allele (defined as non-risk patients) and HCs. Supernatant IL-12p40 and IL-12p70 levels from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.044 and p=0.032, respectively) or those of HCs (p=0.032 and p=0.0015, respectively). Supernatant IL-23 from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.04).

Conclusions IL-12p40 and IL-12p70 but not IL-23 may play an important role in pathophysiology of TAK, and the risk allele of rs6871626 could contribute to production of these cytokines.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.