Systemic levels of biomarkers of inflammation, chemoattraction, cell activation, tissue destruction and tissue repair per cluster
| Cluster 1: | Cluster 2: | Cluster 3: | Cluster 4: | |
| lower-level cluster I | lower-level cluster II | higher-level cluster I | higher-level cluster II | |
| Patients, n | 64 | 64 | 46 | 39 |
| Acute phase proteins and complement system | ||||
| Complement C3, mg·mL−1 | 1.2±0.2 | 1.1±0.2 | 1.3±0.2 | 1.5±1.0 |
| CRP, ng·mL−1 | 3011±2795 | 1773±1859 | 8214±8153 | 9725±8480 |
| Fibrinogen, μg·mL−1 | 6417±2826 | 6870±4533 | 6465±2374 | 8879±7911 |
| Serum amyloid A, ng·mL−1 | 3059±2705 | 1889±1403 | 6239±7311 | 10 745±7810 |
| Cytokines and chemokines and their receptors | ||||
| Eotaxin-2, pg·mL−1 | 1022±632 | 1398±940 | 1371±954 | 1337±965 |
| IL-1β, pg·mL−1 | 4.8±1.2 | 4.3±1.3 | 4.2±1.1 | 5.0±1.6 |
| IL-12 subunit p40, ng·mL−1 | 0.6±0.2 | 0.5±0.1 | 0.5±0.1 | 0.6±0.1 |
| IL-23, ng·mL−1 | 1.4±0.4 | 1.2±0.3 | 1.2±0.3 | 1.4±0.3 |
| IL-6, pg·mL−1 | 2.9±1.6 | 1.9±1.7 | 3.4±1.7 | 6.3±8.2 |
| IL-8, pg·mL−1 | 12±5 | 13±5 | 14±6 | 14±5 |
| IFN-γ-inducible T-cell α-chemoattractant, pg·mL−1 | 43±22 | 44±24 | 55±25 | 64±47 |
| IFN-γ-inducible protein-10, pg·mL−1 | 93±41 | 73±39 | 90±30 | 142±98 |
| IFN-γ, pg·mL−1 | 0.5±0.3 | 0.4±0.4 | 0.5±0.2 | 1.3±2.6 |
| Macrophage migration inhibitory factor, ng·mL−1 | 0.1±0.1 | 0.1±0.1 | 0.1±0.1 | 0.1±0.1 |
| MCP-1, pg·mL−1 | 511±190 | 469±130 | 606±159 | 513±200 |
| MCP-4, pg·mL−1 | 688±235 | 678±207 | 762±210 | 778±455 |
| T-cell-specific protein RANTES, ng·mL−1 | 19±8 | 23±10 | 31±10 | 25±14 |
| Thymus and activation-regulated chemokine, pg·mL−1 | 524±414 | 636±384 | 784±620 | 770±828 |
| IL-2 receptor-α, pg·mL−1 | 2427±694 | 2020±535 | 2695±927 | 3429±1240 |
| TNF-R2, ng·mL−1 | 6.0±1.6 | 4.9±1.2 | 6.0±1.8 | 9.8±5.0 |
| TNF-R1, pg·mL−1 | 1850±476 | 1531±436 | 1905±588 | 2603±919 |
| Osteoprotegerin, pM | 7.0±1.9 | 6.7±1.1 | 7.2±1.3 | 8.9±2.0 |
| Inhibitors of cytokine signalling | ||||
| IL-1 receptor antagonist, pg·mL−1 | 423±132 | 336±74 | 372±99 | 388±118 |
| Adhesion molecules | ||||
| sICAM-1, ng·mL−1 | 282±76 | 292±76 | 321±102 | 389±113 |
| sVCAM-1, ng·mL−1 | 520±116 | 493±106 | 517±142 | 719±396 |
| Immunoglobulins | ||||
| IgA, mg·mL−1 | 2.9±1.6 | 2.4±1.2 | 3.1±1.4 | 3.6±2.9 |
| IgM, mg·mL−1 | 2.1±1.4 | 1.8±1.9 | 1.7±1.1 | 2.5±4.2 |
| Growth factors | ||||
| Angiopoietin-2, ng·mL−1 | 3.7±1.8 | 3.8±1.3 | 4.4±1.4 | 5.1±1.3 |
| BDNF, ng·mL−1 | 18.1±4.9 | 22±5 | 23±7 | 18±7 |
| Stem cell factor, pg·mL−1 | 397±93 | 330±83 | 354±88 | 473±163 |
| Vascular endothelial growth factor, pg·mL−1 | 242±111 | 258±122 | 354±159 | 290±170 |
| Tissue remodelling | ||||
| α1-Antitrypsim, mg·mL−1 | 1.9±0.3 | 2.0±0.4 | 1.9±0.4 | 2.3±0.6 |
| LAP TGF-β1, ng·mL−1 | 9.4±2.8 | 12±3 | 13±3 | 10±3 |
| MMP-3, ng·mL−1 | 19±14 | 13±7 | 14±7 | 23±16 |
| MMP-9, ng·mL−1 | 147±72 | 130±62 | 153±69 | 159±83 |
| Tissue inhibitor of metalloproteinases-1, ng·mL−1 | 150±23 | 163±27 | 195±30 | 199±65 |
| Hormones and adipokines | ||||
| Adiponectin, μg·mL−1 | 4.4±2.1 | 7.0±3.3 | 5.1±2.7 | 7.4±4.7 |
| Leptin, ng·mL−1 | 14.8±12.3 | 8.2±8.8 | 16.8±14.6 | 13.7±14.8 |
| Erythropoietin, IU·mL−1 | 11.3±5.2 | 8.4±2.6 | 11±7 | 13±4 |
| Osteocalcin (OCN/BGLAP), ng·mL−1 | 117±20 | 127±18 | 116±17 | 135±25 |
| Coagulation | ||||
| α2-Macroglobulin (A2Macro), mg·mL−1 | 1.7±0.4 | 1.7±0.4 | 1.7±0.6 | 1.9±0.7 |
| Factor VII, ng·mL−1 | 447±140 | 406±99 | 403±127 | 422±119 |
| PAI-1, ng·mL−1 | 195±45 | 228±53 | 290±56 | 220±112 |
| Plasma carrier proteins | ||||
| Fetuin A, μg·mL−1 | 574±292 | 706±364 | 603±303 | 652±420 |
| Haptoglobin, mg·mL−1 | 1.7±0.9 | 1.6±1.1 | 2.9±1.4 | 3.5±3.1 |
| IGFBP-1, ng·mL−1 | 2978±2432 | 4368±2771 | 3204±2178 | 4504±2870 |
| IGFBP-2, ng·mL−1 | 79±34 | 110±53 | 80±35 | 132±45 |
| Vitamin D-binding protein, μg·mL−1 | 288±108 | 300±91 | 291±122 | 396±727 |
| Other | ||||
| Ferritin, ng·mL−1 | 180±142 | 151±128 | 190±160 | 183±203 |
| β2-Microglobulin, μg·mL−1 | 2.1±0.5 | 1.8±0.3 | 2.1±0.4 | 2.9±1.0 |
| Myoglobin, ng·mL−1 | 69±37 | 74±111 | 54±28 | 96±62 |
| Osteonectin, ng·mL−1 | 1145±344 | 1394±230 | 1720±322 | 1318±394 |
| Osteopontin, ng·mL−1 | 22±7 | 22±8 | 22±7 | 36±14 |
| Bilirubin, mmol·L−1 | 11.6±4.9 | 14±6 | 10±5 | 12±3 |
| Leukocytes, ×109 cells·L−1 | 6.7±1.4 | 6.9±1.9 | 8.1±1.4 | 8.5±2.4 |
| LDL, mmol·L−1 | 2.7±0.9 | 3.1±0.9 | 3.2±1.2 | 2.9±1.0 |
| HDL, mmol·L−1 | 1.7±0.4 | 1.7±0.5 | 1.7±0.5 | 1.5±0.5 |
Data are presented as mean±sd. Eight biomarkers were measured, but excluded from the statistical analysis, because of >30% missing values (B-lymphocyte chemoattractant, eotaxin-1, eotaxin-3, interleukin (IL)-1α, IL-12 subunit p70, IL-15, IL-17 and major histocompatibility complex (MHC) class I chain-related protein-A). ▪ A significantly higher level compared to the remaining three clusters (p-value <0.01); ▪ a tendency for a significantly higher level compared to the remaining three clusters (p-value between 0.05 and 0.01); ▪ a significantly lower level compared to the remaining three clusters (p<0.01); ▪ a tendency for a significantly lower level compared to the remaining three clusters (p-value between 0.05 and 0.01). CRP: C-reactive protein; IFN: interferon; MCP: monocyte chemotactic protein; TNF-R: tumour necrosis factor receptor; BDNF: brain-derived neurotrophic factor; sICAM: soluble intercellular adhesion molecule; sVCAM: soluble vascular adhesion molecule; LAP TGF-β1: latency-associated peptide of transforming growth factor-β1; MMP: matrix metalloproteinase; PAI: plasminogen activator inhibitor; IGFBP: insulin-like growth factor-binding protein; LDL: low-density lipoprotein; HDL: high-density lipoprotein.