SAT0225 TARGETED SERUM METABOLIC PROFILE IN PATIENTS WITH TAKAYASU ARTERITIS
Authors: Dinesh Kumar, Harikrishnan Gangadharan Nair, Avinash Jain, Anupama Guleria, Umesh Kumar, Durga Misra, Ramnath Misra
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Takayasu arteritis (TAK) is a chronic inflammatory arteritis that mainly affects aorta and, its major branches. Often the course is unpredictable and it remains a challenge to assess disease activity despite the availability of acute phase reactants and imaging modalities [1]. Management heavily relies on physician global assessment. Analysis of serum metabolites using nuclear magnetic resonance spectroscopy is a promising exploratory approach towards identifying new biomarkers in TAK which may cast some light on disease pathogenesis and disease activity. <h3>Objectives:</h3> Aim of the study was to evaluate the performance of serum amino acids as determinants of disease activity in TAK. <h3>Methods:</h3> Patients with TAK fulfilling ACR 1990 criteria were enrolled and disease activity assessed using ITAS2010 and ITAS-A[2]. Samples were analysed using 1D 1H 800 MHz Nuclear magnetic resonance spectrometer equipped with a Cryoprobe (at 300 K). The spectra were processed and the concentration of amino acids were measured with respect to internal reference metabolite formate assuming its concentration 10 μM in commercial software program CHENOMX (www.chenomx.com) and the resulted normalized values were compared using Tukey's multiple comparison test and diagnostic potential was evaluated using receiver operating characteristic (ROC) curve analysis. <h3>Results:</h3> 45 active TAK patients with ITAS-A ≥ 4 and 53 inactive TA patients with median age 27 years [IQR, 22-35 and IQR, 23-37 years respectively] were enrolled. Female to male (F:M) ratio was 3.5:1 and 4.9:1 and median duration of illness 5 [IQR, 2-9 years] and 3 [IQR, 1-6 years] years in active and inactive group respectively. Majority had class V disease. 43 individuals served as health control(HC) with mean age 30 years and F:M ratio of 4.3:1. Serum levels of Phenylalanine (Phe), Tyrosine (Tyr), Histidine (His), Valine (Val) and Alanine (Ala) were found to be decreased in TAK patients suggesting augmented utilization in the immune-metabolic pathways mainly to replenish the energy demand and self-repair mechanism under conditions of inflammation and oxidative stress. An analysis of amino acids ratio revealed significantly higher His/Tyr, Ala/Tyr and Val/Tyr ratio in HC when compared to active TAK patients. Ratio were lower in active TAK when compared to inactive TAK patients but only Val/Tyr ratio was significant (AUROC, 0.64 and p, 0.01). Ratio served as a gradient with lowest value in active disease and gradually increasing and moving towards HC as disease was getting controlled <h3>Conclusion:</h3> The present targeted NMR based metabolomics study demonstrated that the serum metabolic profiles of amino acid may help guide therapy and ratio of Val/Tyr can differentiate active from inactive patients. However, future studies on large patient cohorts are required to establish its clinical utility. <h3>References</h3> [1] Nakagomi D, Jayne D. Outcome assessment in Takayasu arteritis. Rheumatol. (United Kingdom) 2016;55:1159–71. [2] Misra R, Danda D, Rajappa SM, Ghosh A, Gupta R, Mahendranath KM, et al. Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatol. (United Kingdom) 2013;52:1795–801. <h3>Disclosure of Interests:</h3> None declared