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Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis

Campochiaro, C; Lytton, S; Nihtyanova, S; Fuchs, D; Ong, VH; Denton, CP; (2019) Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis. Clinical Immunology , 199 pp. 18-24. 10.1016/j.clim.2018.12.009. Green open access

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Abstract

Systemic sclerosis (SSc) is a systemic disease characterized by vasculopathy, progressive fibrosis and autoimmune activation. Tryptophan (Trp) metabolism has been linked to altered immune cell function and to malignancy. We have investigated the role of Trp metabolic pathway in SSc measuring serum Trp, Kynurenine (Kyn) and Trp/Kyn ratio in a cohort of 97 SSc patients and 10 healthy controls. Association with disease characteristics was evaluated. We found that Trp levels in SSc patients were significantly lower compared to HCs. We also found that patients with diffuse cutaneous (dcSSc) had lower levels of Trp compared to limited cutaneous (lcSSc). These results were paralleled by higher levels of Kyn found in SSc patients compared to HCs and significantly lower levels in dcSSc compared to lcSSc. The autoantibody profile was also found to be significantly associated with Kyn and Trp levels as anti-RNA-polymerase III (ARA) positive patients were shown to have lower Trp levels and higher Kyn levels compared with anti-centromere and anti-topoisomerase I positive patients. Moreover, the highest Trp/Kyn was found in ARA+ patients with dcSSc, suggesting that an activation of the Kyn pathway, is more specifically associated with this subset of SSc patients. Stability over time makes these markers of Trp metabolism feasible for SSc stratification.

Type: Article
Title: Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.clim.2018.12.009
Publisher version: http://doi.org/10.1016/j.clim.2018.12.009
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Anti-RNA-polymerase III, Cancer, Kynurenine, Scleroderma, Systemic sclerosis, Tryptophan
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10069204
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