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