TABLE 4.
Potential metabolite biomarkers for diagnosis and classification of SSc.
| Sample type | Analytical technique | Metabolites | ROC curve | Validation | Study | |
|---|---|---|---|---|---|---|
| SSc | Serum | H-NMRS | Aspartate | AUC: 0.81 (CL 95% 0.7–0.93) | NR | Murgia et al. (2018) |
| GC-MS a | Alanine Citrate | |||||
| UHPLC-Q-TOF-MS | L-tryptophan | AUC 0.884 (CI 95% 0.788–0.981) | NR | Meier et al. (2020) | ||
| 1-methyl-adenosine | AUC 0.822 (CI 95% 0.705–0.939) | |||||
| L-tyrosine | AUC 0.812 (CI 95% 0.667–0.958) | |||||
| Urine | HPLC-Q-TOF -MS | N1-methyl-4-pyridine-3-carboxamide | AUC: 0.818 (CI 95% 0.709–0.903 | NR | Fernández-Ochoa ÁQuirantes-Piné et al. (2019) | |
| N1-methyl-2-pyridine-5-carboxamide | AUC 0.766 (CI 95% 0.674–0.858) | |||||
| D-sorbitol | AUC: 0.802 (CI 95% 0.688–0.881) | |||||
| 2,6 Dimethyl-heptonoylcarnitine | AUC: 0.778 (CI 95% 0.67–0.86) | |||||
| Plasma | HPLC-Q-TOF -MS | Alpha- N-phenylacetyl-L-glutamine | AUC. 0.766 (CI 95% 0.656–0.86) | NR | Fernández-Ochoa ÁQuirantes-Piné et al. (2019) | |
| 1-arachidonoylglycerol monoacylglycerol (20:4) Monoacylglycerol (20:5) | AUC: 0.793 (CI95% 0.687–0.875) | |||||
| AUC: 0.748 (CI 95% 0.64–0.858) | ||||||
| dcSSc | Serum | UHPLC-Q-TOF-MS | 1-Palmitoyl-sn-glycero-3-phosphocholine | AUC 0.650 b | NR | Sun et al. (2022) |
| Trans-dehydroandrosterone | AUC 0.720 b | |||||
| Betaine | AUC 0.771 b | |||||
| 1-stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine | AUC 0.725 b | |||||
| H-NMRS GC-MS a | Acetate | AUC: 0.84 (CI 95% 0.7–0.98) | NR | Murgia et al. (2018) | ||
| Fructose | ||||||
| Glutamate | ||||||
| Glutamine | ||||||
| Glycerol | ||||||
| Glutarate | ||||||
| PAH | Serum | HPLC-FLD | Asymmetric dimethylarginine | AUC 0.86 (CI 95% 0.7–1.0) | NR | Thakkar et al. (2016) |
| Symmetric dimethylarginine | AUC 0.88 (CI 95% 0.74–1.0) | |||||
| Progressive ILD | Serum | UHPLC-Q-TOF-MS | L-Leucine | AUC 0.847 (CI 95% 0.695–1.00) | External validation Paris Cohort | Meier et al. (2020) |
| L-Isoleucine | AUC 0.826 (CI 95% 0.656–0.997) | Progressive SSc-ILD (n = 7) | ||||
| Adenosine monophosphate | AUC 0.785 (CI 95% 0.598–0.971) | Controls (n = 27) | ||||
| Xanthosine | AUC 0.771 (CI 95% 0.551–0.9) | |||||
| ILD | Serum | UHPLC-Q-TOF-MS | Ile-Ala | AUC 0.807 b | NR | Sun et al. (2022) |
| L-Glutamine | AUC 0.756 b | |||||
| Androsterone sulfate | AUC 0.778 b |
Detector is not specified in the document.
IC, 95% Not reported.
Abbreviations: SSc, Systemic sclerosis; dcSSc, diffuse cutaneous systemic sclerosis; PAH, pulmonary arterial hypertension; ILD, interstitial lung disease; H NMRS, proton nuclear magnetic resonance spectrometry; GC-MS, Gas chromatography-mass spectrometry; UHPLC-Q-TOF-MS, Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry; HPLC-Q-TOF-MS, high-performance liquid chromatography quadrupole time-of-flight mass spectrometry; HPLC-FLD, High-performance liquid chromatography with fluorescence detection; ROC, receiver operating characteristic curve; AUC, area under the curve; NR, not reported.