Investigated potential biomarkers and their correlations to disease activity
| Concentration* | P value† | Spearman’s correlation‡ | ||||
| Controls (n=322) | SLE (n=437) | Control vs SLE | SLAM4 (n=437) | SLEDAI-2K2 (n=437) | PtGDA§ (n=132) | |
| Cytokines¶ | ||||||
| INF-γ | 6.1 (4.6–9.9) | 11.7 (7.0–20.2) | <0.001 | 0.08 (p=0.08) | 0.14 (p=0.005) | 0.07 (p=0.4) |
| IL-8 | 3.0 (2.2–4.0) | 4.9 (3.1–8.7) | <0.001 | 0.16 (p<0.01) | 0.16 (p<0.01) | 0.23 (p<0.01) |
| IL-15 | 2.1 (1.8–2.4) | 2.9 (2.3–4.1) | <0.001 |
0.28 (p<0.01) |
0.28 (p<0.01) | 0.19 (p=0.03) |
| Eotaxin | 88.4 (70.1–113.8) | 133.5 (97.6–186.0) | <0.001 | 0.07 (p=0.14) | 0.04 (p=0.4) | 0.14 (p=0.1) |
| MCP-1 | 69.0 (55.0–85.0) | 109.5 (83.0–152.5) | <0.001 | 0.23 (p<0.01) | 0.23 (p<0.01) |
0.28 (p<0.01) |
| MDC | 939.0 (764.3–1109) | 844.0 (640.3–1120) | 0.002 | −0.10 (p=0.04) | −0.17 (p<0.01) | −0.16 (p=0.06) |
| MIP-1β | 43.8 (33.4–56.4) | 72.7 (50.8–108.1) | <0.001 | 0.18 (p<0.01) | 0.20 (p<0.01) | 0.20 (p=0.02) |
| IL-10 | 0.3 (0.2–0.4) | 0.8 (0.5–1.5) | <0.001 | 0.20 (p<0.01) |
0.27 (p<0.01) | 0.18 (p=0.04) |
| IL-6 | 0.6 (0.5–0.9) | 1.2 (0.7–2.2) | <0.001 | 0.23 (p<0.01) | 0.24 (p<0.01) |
0.30 (p<0.01)) |
| TNF-α | 2.3 (2.0–2.8) | 4.5 (3.1–6.2) | <0.001 |
0.34 (p<0.01) |
0.32 (p<0.01) |
0.29 (p<0.01) |
| IL-12/IL-23p40 | 131.0 (99.5–179.0) | 181.0 (123.0–286.0) | <0.001 | 0.07 (p=0.12) | 0.08 (p=0.11) | −0.05 (p=0.6) |
| IL-16 | 182.0 (147.0–225.0) | 214.0 (152.0–287.0) | <0.001 | 0.14 (p<0.01) | 0.19 (p<0.01) | 0.13 (p=0.2) |
| IL-1α | 6.4 (3.4–11.7) | 6.3 (3.2–12.8) | 0.6 | 0.05 (p=0.4) | 0.19 (p<0.01) | −0.06 (p=0.5) |
| IL-7 | 3.7 (2.5–5.5) | 5.0 (3.2–8.7) | <0.001 | 0.11 (p=0.03) | 0.16 (p<0.01) | 0.10 (p=0.2) |
| VEGF | 56.7 (40.9–81.6) | 77.1 (47.7–123.5) | <0.001 | 0.11 (p=0.03) | 0.23 (p<0.01) | 0.16 (p=0.07 |
| Eotaxin-3 | 20.8 (14.9–25.7) | 24.4 (19.3–35.1) | 0.0008 | 0.02 (p=0.8) | 0.08 (p=0.3) | −0.01 (p=0.9) |
| IP-10 | 352.0 (258.8–479.0) | 725.0 (446.0–1309) | <0.001 | 0.19 (p<0.01) | 0.23 (p<0.01) |
0.27 (p=0.002) |
| MCP-4 | 56.0 (41.0–80.8) | 78.0 (53.8–124.0) | <0.001 | −0.01 (p=0.8) | −0.03 (p=0.6) | 0.04 (p=0.6) |
| MIP-1α | 12.0 (8.8–17.6) | 21.5 (17.3–28.6) | <0.0001 |
0.27 (p<0.01) |
0.26 (p<0.01) | 0.10 (p=0.3) |
| TARC | 54.4 (37.4–84.8) | 85.3 (51.9–150.3) | <0.001 | 0.03 (p=0.5) | 0.04 (p=0.4) | 0.04 (p=0.6) |
| Standard clinical laboratory measurements | ||||||
| ESR | 8.5 (5-13) | 19 (11-34) | <0.0001 |
0.48
(p<0.01) |
0.28 (p<0.01) | 0.18 (p=0.04) |
| C4 | 0.21 (0.17–0.25) | 0.15 (0.1–0.2) | <0.0001 | −0.12 (p=0.01) |
−0.36
(p<0.01) | −0.10 (p=0.3) |
| C3 | 1.04 (0.9–1.2) | 0.88 (0.7–1.0) | <0.0001 | −0.10 (p<0.05) |
−0.31
(p<0.01) | −0.02 (p=0.8) |
| P-albumin | 42 (41-44) | 39 (36-41) | <0.0001 |
−0.31 (p<0.01) |
−0.33 (p<0.01) |
−0.42 (p<0.01) |
| hsCRP | 0.93 (0.4–2.1) | 1.7 (0.7–5.3) | <0.0001 | 0.21 (p<0.01) | 0.16 (p<0.01) |
0.25 (p<0.01) |
| anti-dsDNA | 4 (4.0–4.0) | 5 (4.0–19.5) | <0.0001 | 0.21 (p<0.01) |
0.47
(p<0.01) | 0.19 (P=0.03) |
| U-albumin/creatinine | 0.45 (0.32–0.76) | 1.11 (0.52–5.48) | <0.0001 | 0.22 (p<0.001) |
0.30 (p<0.001) | 0.12 (p=0.2) |
Concentrations of investigated potential biomarkers and u-albumin/creatinine in patients with SLE and controls, their p values comparing SLE and controls and their correlations to three different measurements of disease activity are reported. Biomarkers with correlations (ρ)≥|0.25| to all three disease activity measurements are highlighted in bold. Italic numbers indicates biomarkers which are included in the respective indices.
*Median (25% quantile–75% quantile). Concentrations of cytokines are reported in pg/mL. Standard clinical laboratory measurements reported as ESR in mm/hour, Complement factor C4 in g/L, Complement factor C3 in g/L, plasma albumin (p-albumin) in g/L, high-sensitivity (hs) CRP in mg/L, anti-dsDNA units and urinary (u) albumin/creatinine ratio in mg/mmol.
†Mann Whitney U test. Not compensated for multiple testing (variables: n=26).
‡Spearman’s correlation rho (p value). Spearman’s ρ>0.25 are highlighted in bold. Spearman’s ρ=|0.20–0.39| is considered as week correlation and ρ=0.40–0.59 as moderate correlation.
§PtGDA, Patients Global Disease Activity as determined by SLAQ.7
¶The numbers of missing values are reported in online supplementary table S1 (all cytokines except IL-10, IL-6, Eotaxin-3 and MIP-1α were detected in more than 90% of cases). Data below LLOQ were treated as missing values.
ESR, erythrocyte sedimentation rate; LLOQ, lower limit of quantification; SLAM, SLE Activity Measure; SLAQ, Systemic Lupus Activity Questionnaire; SLE, systemic lupus erythematosus; SLEDAI-2K, SLE Disease Activity Index; VEGF, Vascular endothelial growth factor.