Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with inflammation in systemic sclerosis (115.5)

Abstract

Abstract Background. A contributory effect of IDO1 to inflammatory autoimmune pathologies such as rheumatoid arthritis and systemic lupus erythematosus has been recently described. We aimed to address whether IDO1-driven kynurenine (KYN) production correlates with degree of inflammation and disease extent in systemic sclerosis (SSc). Methods. Peripheral blood was obtained from 27 consecutive patients (median age 62 years, range 22-78; median disease duration = 10 months, range 1-35) with either limited cutaneous SSc (n=17) or diffuse cutaneous SSc (n=10). In 11 of the 27 patients, CD19+ B cells were magnetically purified to estimate IDO1 mRNA levels by quantitative PCR. Results. High serum KYN in SSc (3.17±0.82 μM compared with 1.82±0.37 μM in healthy controls; p<0.0001) positively correlated with serum CRP (r=0.42; p=0.03), an established marker of inflammation. We showed a trend towards higher KYN levels in diffuse SSc compared with limited SSc, although no correlations emerged between KYN release and serological features or lung fibrosis. Interestingly, purified CD19+ B cells expressed IDO1 mRNA, whose copy number correlated with serum CRP (r=0.58; p=0.048) and with the frequency of bona fide CD4+FoxP3+ Treg cells. Conclusions. The generation of KYN and expansion of Treg cells may reflect a counter-regulatory mechanism to limit excessive inflammation in SSc.