AB0149 Activation of indoleamine 2, 3-dioxygenase 1 (ido1) in patients with systemic sclerosis. (23rd January 2014)

• Record Type: Journal Article
• Authors: Del Papa, N.; Filippini, P.; De Cristofaro, R.; Sambataro, D.; Rovelli, F.; Vitali, C.; Locatelli, F.; Rutella, S.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A831
• Page End: A831
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.2472
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: IDO1 degrades tryptophan (TRP) into intermediates with immune-modulating activities and endothelium-relaxing properties, collectively referred to as kynurenines (KYN). A contributory effect of IDO1 to inflammatory autoimmune pathologies, such as rheumatoid arthritis and systemic lupus erythematosus, has been recently described. Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by vascular abnormalities and diffuse fibrosis in skin and internal organs. Objectives: We aimed to address whether IDO1-driven kynurenine (KYN) production correlates with degree of inflammation and clinical features in SSc patients. Methods: Peripheral blood was obtained from 70 consecutive adult patients with SSc. Serum KYN and TRP levels were measured with RP-HPLC. Pro-angiogenic hepatocyte growth factor (HGF) and placental growth factor (PlGF) were quantitated with ELISA. Results: Serum KYN levels were higher in SSc compared with healthy controls (2.55±1.47 μM versus 1.74±0.30 μM; p=0.018) and positively correlated with serum C-reactive protein (r=0.35, p=0.0042) and erythrocyte sedimentation rate (r=0.26, p=0.037), but not with HGF or PlGF levels, complement C3 or C4 levels, presence of skin ulcers, modified Rodnan skin score (MRSS) or disease activity score. Interestingly, KYN levels positively correlated with pulmonary arterial pressure (r=0.38; p=0.017). However, KYN levels were superimposable in patients with normal chest CT findings and in those with clinical and radiographic evidence of alveolitis or lung fibrosis. Conclusions: The generation of KYN is heightened in SSc patients and it could be related to the activation of counter-regulatory mechanisms of both inflammation (related to the production of pro-inflammatory cytokines) and vasoconstriction. The role played by KYN in promoting autoimmune circuits in SSc remains to be elucidated. Disclosure of Interest: None Declared