Background/Purpose:

Takayasu Arteritis (TA), a large vessel disease of unknown aetiology, is the orphan of the inflammatory vasculitides with no evidence base for therapy. It often presents with vessel occlusions and biomarkers are needed for this subclinical process. Limited knowledge of its pathogenesis has hindered finding good candidates but PET scans indicate an active metabolic process in the aortic wall. Here, we have applied NMR-based serum metabolomics to gain more basic understanding of this process. The serum metabolic profiles of TA patients, Systemic lupus erythemoatosus (SLE) patients (chosen here as a diseased control group) and normal controls (NC) were obtained and compared using multivariate statistical data analysis.

Methods:

The sera samples were collected from (a) 29 TA patients fulfilling the ACR criteria seen at first presentation in SGPGI, Lucknow and assessed for disease activity and extent using ITAS and DEI.Tak., (b) 30 SLE patients attending the OPD and (c) 30 healthy age/sex-matched normal controls (NC) from the local community. NMR experiments were performed at 298 K on Bruker Avance III 800 MHz NMR spectrometer and metabolic differences between TA, SLE and NC were identified using multivariate statistical analysis.

Results: The projection to least squares discriminant analysis (PLS-DA) showed 100% specificity and sensitivity in differentiating TA from NC regardless of TA type and disease activity. Compared to healthy controls, the TA patients had (a) increased serum levels of choline metabolites, LDL cholesterol, N-acetyl glycoproteins (NAGs), and glucose and (b) decreased serum levels of lactate, lipids, HDL cholesterol, glucogenic amino acids (such as alanine, valine, arginine, proline, histidine, glutamine, etc.). We also accessed the role of disease activity on serum metabolic profiles in 2 ways. Spectra from 12 TA clinically active at 1^st visit were not significantly different from 17 inactive (r²=0.13) but did differ clearly from 6 who had become inactive at follow-up r²=0.98). PLS-DA model also clearly separated TA from SLE (chosen as a disease control with known vascular inflammatory components  suggesting that the TA results do not simply reflect active inflammation. Compared to SLE patients, the serum levels of lipid (mainly VLDL) and choline metabolites were found to be elevated in TA patients indicating the phospholipid and choline metabolism more activated in TA. 

Conclusion: NMR based serum metabonomics study revealed a distinctive signature of TA, in particular the choline metabolites were found to be significantly higher in TA as compared to NC and SLE. However, the results of this study are preliminary and need to be confirmed in a prospective study using a larger cohort of TA patients and disease control like small vessel disease (SVV) to assess the specificity and utility of the metabolomic signature.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nmr-based-metabolomics-provides-new-insights-into-the-inflammatory-processes-in-takayasu-arteritis/