Background The enzymes IDO degrades Trp into Kyn and is induced by IFN-gamma/IL-1. Neo is produced by monocytes/macrophages after IFN-gamma stimulation through the enzyme GTPCH and is a biomarker for monitoring immune activation in several diseases . The activity of GTPCH is induced in parallel to IDO and the Kyn/Trp ratio has been suggested to be a direct measure of IDO activity .
Objectives To assess serum level of Kyn, Trp, Neo and Kyn/Trp ratio in SSc and potential associations with specific disease features.
Methods 60 SSc pts and 10 healthy controls (HC) were recruited and serum levels of Kyn, Trp and Neo were measured. Kyn/Trp ratio was calculated. The results were then correlated with specific disease features: disease duration, limited or diffuse disease, autoantibody profile (anti-RNA pol III (ARA), anti-topoisomerase (ATA) and anti-centromere (ACA)), inflammatory markers, Hb level, concurrent modified Rodnan skin score (mRSS), peak mRSS, pulmonary fibrosis (PF), pulmonary arterial hypertension (PAH), history of scleroderma renal crisis (SRC), GI involvement, vasculopathy, environmental exposure, oncology history, smoking status, immunosuppressive treatment, NT-proBNP and urate levels. Non-parametric statistical tests were used.
Results Kyn/Trp ratio was higher in SSc compared to HC (mean 49.97±32.77 [41.50 – 58.43] vs 22.5±6.3 [13.5 – 32.5] μmol/mmol, p<0.05) and, more specifically, dcSSc showed higher ratio compared to lcSSc that had higher ratio than HC (mean 56.58±39.62 [43.18 – 69.99] vs 40.05±13.93 [34.16 – 45.93] vs 22.5±6.3 [17.99 – 27.01] μmol/mmol respectively, p<0.05). Moreover, ARA+SSc had a significantly higher ratio compared to ATA+ and ACA+pts (mean 61.24±41.40 [45.78 – 76.70] vs 39.62±17.99 [29.66 – 49.58] and 37.77±10.20 [32.12 – 43.42] μmol/mmol respectively, p<0.05). Kyn/Trp ratio was significantly correlated with SRC (p<0.05). We found a direct correlation with mRSS (r=0.269, p<0.05), peak mRSS (r=0.276), urate level (r=0.376), CRP (r=0.285) and ESR (r=0.320). Conversely, Neo levels, although significantly higher in SSc compared to HC (mean 12.63±9.30 [10.21 – 15.06] vs 7.11±3.31 [4.74 – 9.48] nmol/L, p<0.05), were not significantly different in diffuse compared to limited SSc, but were higher in ARA+ compared to ACA+ and ATA+ patients (mean 14.93±11.52 [10.54 – 19.31] vs 10.81±4.95 [8.07 – 13.56] vs 10.02±6.83 [6.24 – 13.80] respectively, p<0.05). Neo levels significantly correlated with PAH. A direct correlation (p=0.05) was found with CRP (r=0.471) and ESR (r=0.430).
Conclusions These data suggest that Kyn/Trp ratio and Neo levels may reflect aetio-pathogenetic mechanisms in SSc and be elevated in the subgroup of dcSSc that are ARA+, or those manifesting SSc complications associated with ARA+. A specific IFN-gamma signature could be thought to be responsible for the higher levels found in patients although larger studies are required.
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Disclosure of Interest None declared