Circulatory histidine levels as predictive indicators of disease activity in takayasu arteritis

Quantitative assessment of disease activity is important for effective management of patients with autoimmune inflammatory diseases (AIDs) including Takayasu arteritis (TA).  Histidine supplementation alleviates inflammation and has strong anti-oxidative effects as well. The present study aims to evaluate the diagnostic potential of circulatory histidine for predicting disease activity in TA.

The serum metabolic profiles on 98 TA-patients and 77 normal controls (NC) samples were measured at high-resolution 800 MHz NMR spectrometer employing standard 1D-¹H-CPMG NMR experiments. The NMR spectral data were processed and concentrations of histidine and other circulatory metabolites were estimated with respect to formate (as an internal reference) and compared using ANOVA based on Tukey's multiple comparison test and statistical significance was considered at P-value < 0.05. The correlations of histidine with plasma CRP and ESR levels were evaluated using Spearman-r method. Data were expressed as median (interquartile-range [IQR]).

Histidine levels were significantly decreased in active TA patients (23.90; IQR:16.10) compared to both inactive TA patients (35.50, IQR:24.30) and NC (42.80, IQR:22.10), whereas there was no significant difference between inactive TA and NC. For TA patients, the histidine levels correlated negatively with clinical markers of inflammation, that is, ESR (r = -0.19, P < .078) and with the CRP (r = -0.26, P < .013). Further, the receiver-operating-characteristic (ROC) curve analysis was performed to test the diagnostic potential of histidine for differentiating active from inactive disease. The area under the ROC curve (AUROC) value equal to 0.65 [95% CI = 0.54-0.76] revealed its moderate discriminatory ability. Compared to other circulatory metabolites, the discriminatory performance of histidine was also found to be in the moderate range (highest AUROC-value of 0.76 was found for glutamine-to-glucose ratio (QGR).

The study demonstrated the altered circulatory histidine levels in TA patients that may serve as a surrogate marker for improving the diagnostic screening of active and inactive TA patients.