Abstract
Diagnosing Behcet’s disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.
Highlights
Behcet’s disease (BD), called Behcet’s syndrome, is a rare systemic vasculitis that is characterized by common symptoms of recurrent oro-genital ulceration, skin lesions, arthritis and uveitis [1,2,3]
We evaluated the feasibility of employing urine metabolomic biomarker panels for reliable diagnosis of BD
Unsupervised principal component analysis (PCA) with 109 metabolites was carried out to obtain an overview of the urinary GC/TOF−MS data from BD patients and healthy controls (HC) group
Summary
Behcet’s disease (BD), called Behcet’s syndrome, is a rare systemic vasculitis that is characterized by common symptoms of recurrent oro-genital ulceration, skin lesions, arthritis and uveitis [1,2,3]. Diagnosis of BD is only based on the clinical symptoms because no sensitive and specific relevant biologic tests are available. Because it may take months or even years for all the common symptoms to appear, the diagnosis of BD based on clinical criteria may not be made for long time. In view of these aspects, the marked importance of investigating new diagnostic biomarkers that allow reliable and early diagnosis of BD is highlighted. We evaluated the feasibility of employing urine metabolomic biomarker panels for reliable diagnosis of BD
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