TABLE 1.
Characteristics of studies included in the systematic review.
| Sample type | Sample size | Gender (M/F) | Age average (years) | Analytical technique | Altered metabolites in SSc vs. HC | Study |
|---|---|---|---|---|---|---|
| Plasma | SSc: 27 | 4/23 | 56.9 | GC-MS a | Increased: Nitrate | Neumann Andersen et al. (2000) |
| Controls: 27 | Decreased: NR | |||||
| SSc: 71 | 10/61 | 58.5 | HPLC-FLD | Increased: Homocysteine | Caramaschi et al. (2003) | |
| Controls: 30 | Decreased: NR | |||||
| SSc: 15 | NR | 42.2 | GC-MS a | Increased: Malondialdehyde | Tikly et al. (2006) | |
| Controls: 13 | Decreased: NR | |||||
| SSc: 60 | 4/56 | 54.6 | HPLC-FLD | Increased: Homocysteine | Caramaschi et al. (2007) | |
| Controls: 30 | Decreased: NR | |||||
| SSc: 40 | 38/2 | 58.4 | HPLC-MS a | Increased: NR | Atteritano et al. (2016) | |
| Controls: 40 | Decreased: Vitamin D | |||||
| SSc: 59 | 7/52 | 56.5 | UHPLC-Q-TOF-MS | Increased: DL-2-aminooctanoic acid, Diacylglycerol 38:5, 1-(9Z-pentadecenoyl)-glycero-3-phosphate, phosphatidylcholine 36:4, 2,4-dinitrobenzenesulfonic acid, alpha-N-phenylacetyl-l-glutamine | Bellocchi et al. (2018) | |
| Controls: 28 | Decreased: NR | |||||
| SSc: 20 | 3/17 | 57 | UHPLC-Orbitrap-MS | Increased: Lauric acid, myristic acid, arachidic acid, carnitine, isovaleryl-carnitine | Ottria et al. (2020) | |
| Controls: 7 | Decreased: Octanoyl-carnitine, palmitoyl-carnitine | |||||
| SSc: 42 | 7/35 | 59.9 | HPLC-TQ-MS | Increased: Glutamine, proline, 1-methylhistidine, betaine, methylnicotinamide, asymmetric dimethylarginine | Smolenska et al. (2020) | |
| Controls: 27 | Decreased: Tryptophan | |||||
| SSc: 52 | 8/44 | 60 | HPLC-IM-Q-TOF-MS | Increased: Phosphatidylcholine 34:1, 34:2, 34:3; sphingomyelin 33:1, 35:1, 35:2 | Geroldinger-Simić et al. (2021) | |
| Controls: 48 | Decreased: NR | |||||
| SSc: 52 | 8/44 | 60 | HPLC-IM-Q-TOF-MS | Increased: Kynurenine, dimethylarginine, citrulline, ornithine, phenylacetylglutamine, 1-methylhistidine, 3-methylhistidine | Bögl et al. (2022) | |
| Controls: 48 | Decreased: Tryptophan, OH-tryptophan, alanine, lysophosphatidylcholine 22:4a, 22:4b, 20:2; sphingomyelin 34:1, 40:3 | |||||
| SSc: 59 | 7/52 | 56.5 | HPLC-ESI-QTOF-MS | Increased: Alpha-N-phenyl acetyl-L-glutamine, butyrylcarnitine, valerylcarnitine, 2-4-dinitrobenzenesulfonic acid, oleic acid, 1-arachidonoylglycerol monoacylglycerol (20:4), monoacylglycerol (20:5) | Fernández-Ochoa ÁQuirantes-Piné et al. (2019) | |
| Controls: 28 | Decreased: NR | |||||
| Serum | SSc: 10 | 0/10 | 47 | HPLC-QTRAP-MS | Increased: Arachidonoyl-lysophosphatidic acid, sphingosine 1-phosphate | Tokumura et al. (2009) |
| Controls: 13 | Decreased: NR | |||||
| SSc: 68 | 0/68 | 67.6 | HPLC-TQ-MS | Increased: 17β-estradiol, estrone | Aida-Yasuoka et al. (2013) | |
| Controls: 35 | Decreased: NR | |||||
| SSc: 19 | 3/16 | 55 | GC-TOF-MS | Increased: Aminomalonic acid, arachidonic acid, arginine, aspartic acid, beta-alanine, cholesterol, inositol-1-phosphate, lauric acid, oleamide, ornithine-1,5-lactam, picolinic Acid, pyroglutamic acid, ribose, succinic Acid, urea, uric acid | Bengtsson et al. (2016) | |
| Controls: 18 | Decreased: Alanine, cysteine, lactic acid, malic acid, nonanoic acid, taurine, threonic acid | |||||
| SSc: 37 | 8/29 | 58.7 | H-NMRS GC-MS a | Increased: Glutamine, 3-OH-butyrate | Murgia et al. (2018) | |
| Controls: 20 | Decreased: Citrate, aspartate, alanine, choline, glutamate, glutarate, glycerate, threonate | |||||
| SSc: 97 | 16/81 | 59 | HPLC-FLD | Increased: Kynurenine | Campochiaro et al. (2019) | |
| Controls: 10 | Decreased: Tryptophan | |||||
| SSc: 36 | 6/30 | 61.5 | UHPLC-Q-TOF-MS | Increased: 1-methyladenosine | Meier et al. (2020) | |
| Controls: 12 | Decreased: L-tryptophan, L-tyrosine | |||||
| SSc: 30 | 6/24 | 46.3 | UHPLC-Q-TOF-MS | Increased: Vitamin E, alpha-N-phenylacetyl-L-glutamine, L-glutamine, L-isoleucine, phenol, 2-oxoadipic acid, 1-palmitoyl-2-hydroxy-sn, glycero-3-phosphoethanolamine, chenodeoxycholate, indoxyl sulfate, D-quinovose | Sun et al. (2022) | |
| Controls: 30 | Decreased: 3b-hydroxy-5-cholenoic acid, 1-stearoyl-glycerol, trans-dehydroandrosterone, 4-nonylphenol, norethindrone acetate, cis-9,10-epoxystearic acid, 16-hydroxypalmitic acid, 2-ethyl-2-hydroxybutyric acid, stearic acid, hexadecanedioic acid, 3 hydroxy caproic acid, androsterone sulfate, benzenebutanoic acid, pregnenolone sulfate, arachidonic acid, dodecanoic acid, palmitic acid, myristic acid, cholesterol 3-sulfate, caprylic acid, Cis-(6,9,12)-linolenic acid, alpha-ketocaproic acid, azelaic acid | |||||
| Urine | SSc: 59 | 7/52 | 56.5 | HPLC-Q-TOF-MS | Increased: D-Sorbitol, N-cyclohexylformamide, Ser-Pro-Pro, dihydroxy-1H-indole glucuronide, 2-(2-phenylacetoxy)propinylglycine, alpha-N-phenylacetyl—L glutamine, pyroglutamic acid | Fernández-Ochoa ÁQuirantes-Piné et al. (2019) |
| Controls: 28 | Decreased: N-Methylnicotinamide, proline betaine, creatinine, vinylacetylglycine, N1-methyl-4pyridine-3-carboxamide, N1-methyl-2-pyridine-5-carboxamide, hydroxyprolyl-valine, L-beta-aspartyl-L-Leucine, Hypaphorine, 2-octenoyl-carnitine, decatrienoylcarnitine, 2-nonenoylcarnitine, 2,6-dimethylheptanoyl carnitine, 9-decenoylcarnitine, 9-hydroxydodecenoylcarnitine, undecenoyl carnitine | |||||
| SSc: 11 | 0/11 | 51 | GC-EI-MS | Increased: 15-F-2t-isoprostane | Cracowski et al. (2002) | |
| Controls: 11 | Decreased: NR | |||||
| SSc: 43 | 1/42 | 54.1 | HPLC-UV | Increased: 8-isoprostaglandin-F2a | Volpe et al. (2006) | |
| Controls: 43 | Decreased: NR | |||||
| Exhaled breath | SSc: 46 | NR | 54 | CGC-FID | Increased: Ethane | Cope et al. (2006) |
| Controls: 21 | Decreased: Ethanol |
Detector is not specified in the document.
Increased and decreased metabolites shown in the table correspond to altered metabolites in SSc, patients compared to HC. Abbreviations: SSc, Systemic sclerosis; GC-MS, Gas chromatography-mass spectrometry; HPLC-FLD, High-performance liquid chromatography with fluorescence detection; UHPLC-Q-TOF-MS, Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry; UHPLC-Orbitrap-MS, Ultra-high-performance liquid chromatography coupled with ion trap mass spectrometry; HPLC-TQ-MS, High-performance liquid chromatography coupled to triple-stage quadrupole mass spectrometer; HPLC-IM-Q-TOF-MS, High-performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry; HPLC-ESI-QTOF-MS, High-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry; HPLC-QTRAP-MS, High-performance liquid chromatography quadrupole-linear ion trap hybrid mass spectrometry; GC-TOF-MS, Gas chromatography time-of-flight mass spectrometry; H NMRS, proton nuclear magnetic resonance spectrometry; HPLC-QTOF-MS, High-performance liquid chromatography quadrupole time-of-flight mass spectrometry; GC-EI-MS, gas chromatography electron impact mass spectrometry; HPLC-UV, High-performance liquid chromatography with on-line UV, system; CGC-FID, capillary gas chromatography flame ionization detection; NR, Not Reported.