Table 1.
Clinically Used Biomarkers and Biomarkers under Investigation in SSc-ILD
| Mechanistic Pathway and Biomarker | References |
|---|---|
| Clinically used biomarkers | |
| Immune dysregulation or inflammation | |
| Anti-centromere | 20, 22, 37 |
| Anti–Scl-70 | 22, 37 |
| Nucleolar pattern on ANA (representing anti-Th/To, U3 RNP) | 83 |
| Biomarkers supported by significant clinical data | |
| Epithelial cell injury or barrier dysfunction | |
| CCL-18 | 40, 61 |
| KL-6* | 23, 38, 39 |
| SP-D | 84 |
| Immune dysfunction or inflammation | |
| IL-6/CRP | 12, 41 |
| Biomarkers under investigation | |
| Epithelial cell injury or barrier dysfunction | |
| APOAI | 55 |
| CC16 | 85 |
| ET-1 | 86 |
| Isoprostane | 86 |
| SP-A | 87 |
| sE-selectin | 86 |
| sVCAM-1 | 86 |
| SPFA2 | 55 |
| S100A6 | 55 |
| TGF-β | 86 |
| VEGF | 86 |
| 14-3-3ε | 55 |
| Immune dysfunction or inflammation | |
| Anti-CXCR4 | 48 |
| Anti-CXCR3 | 48 |
| CCL2 | 43 |
| CRP | 88 |
| CXCL4 | 45 |
| CXCL10 | 89 |
| CX3CL1 | 90 |
| C3a | 55 |
| IL-10 | 86 |
| IL-15 | 86 |
| IL-17† | 65 |
| IL-22† | 65 |
| IL-23 | 86 |
| miR-155 | 19 |
| Remodeling and fibrosis | |
| Chitinase-1 | 50 |
| CTGF | 86 |
| Circulating fibrocytes | 88 |
| GDF-15 | 88 |
| MMP7 | 27 |
| MMP12 | 42 |
| MMP13 | 88 |
| miR-21 | 19 |
| miR-92A | 91 |
| miR-200c | 88 |
| PMN elastase | 86 |
| TIMP-1 | 86 |
| TIMP-2 | 88 |
| YKL-40 | 49 |
Definition of abbreviations: 14-3-3ε = tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon; ANA = antinuclear antibody; anti-Th/To = Th/To ribonucleoprotein antibody; APOAI = apolipoprotein A-I; C3a = complement 3 anaphylatoxin; CC16 = club cell secretory protein 16; CCL = chemokine (C-C motif) ligand; CRP = C-reactive protein; CTGF = connective tissue growth factor; CX3CL1 = chemokine (C-X3-C motif) ligand 1; CXCL = chemokine (C-X-C motif) ligand; CXCR3 = chemokine (C-X-C motif) receptor 3; ET-1 = endothelin-1; GDF-15 = growth differentiation factor–15; KL-6 = Krebs von den Lungen-6; miR = microRNA; MMP = matrix metalloproteinase; PMN = polymorphonuclear; S100A6 = S100 calcium-binding protein A6; Scl-70 = topoisomerase 1; sE-selectin = soluble E selectin; SP-A = surfactant protein A; SP-D = surfactant protein D; SPFA2 = pulmonary surfactant–associated protein A2; SSc-ILD = systemic sclerosis–associated interstitial lung disease; sVCAM-1 = soluble vascular cell adhesion molecule 1; TGF-β = transforming growth factor-β; TIMP-1 = tissue inhibitors of metalloproteinases-1; U3 RNP = fibrillarin; VEGF = vascular endothelial growth factor; YKL-40 = chitinase-3-like protein 1.
Approved by Japan’s Health Insurance Program as a diagnostic marker for interstitial lung diseases in 1999.
Circulating IL-producing T cells.