Table 7.
Concentrations of angiogenic mediators in B cell culture supernatants from healthy controls, and SSc patients with and without PAH from the validation cohort.
| Healthy controls vs SSc patients | SSc-no PAH vs SSc-PAH patients | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| HC (N=9) | SSc (N=18) | Effect size | p | SSc-no PH(N=9) | SSc-PAH(N=9) | Effect size | p | ||
|
Angiogenin (pg/mL) median (Q1;Q3) |
No stim | 23.35 (1.28; 25.09) | 29.01 (24.51; 33.30) | 1.36 (0.48; 2.24) | 0.008 | 29.01 (23.40; 31.71) | 29.01 (25.09; 34.86) | 0.21 (-0.72; 1.13) | 0.69 |
| Stim | 25.66 (1.28; 29.01) | 34.08 (29.55; 38.44) | 1.49 (0.60; 2.38) | 0.004 | 31.40 (30.10; 36.41) | 37.43 (29.55; 38.44) | 0.29 (-0.64; 1.21) | 0.57 | |
|
Angiopoietin 1 (pg/mL) median (Q1;Q3) |
No stim | 136.3 (39.20; 156.9) | 167.1 (146.6; 197.7) | 1.15 (0.29; 2.00) | 0.02 | 172.3 (167.1; 197.7) | 156.9 (146.6; 187.6) | -0.33 (-1.26; 0.60) | 0.51 |
| Stim | 105.2 (54.68; 136.3) | 149.2 (146.6; 212.9) | 1.00 (0.16; 1.84) | 0.03 | 146.6 (146.6; 212.9) | 156.9 (136.3; 187.6) | -0.06 (-0.99; 0.86) | 0.93 | |
|
Angiopoietin 2 (pg/mL) median (Q1;Q3) |
No stim | 599.0 (589.4; 612.6) | 606.5 (592.9; 620.4) | 0.05 (-0.75; 0.85) | 0.92 | 608.2 (592.9; 620.4) | 604.9 (595.9; 614.3) | -0.08 (-1.01; 0.84) | 0.89 |
| Stim | 589.4 (577.5; 604.9) | 565.2 (552.9; 595.9) | -0.92 (-1.76; -0.08) | 0.05 | 565.2 (559.1; 612.6) | 565.2 (552.9; 583.6) | -0.37 (-1.30; 0.56) | 0.45 | |
|
ANGPTL-6 (pg/mL) median (Q1;Q3) |
No stim | 106.5 (106.5; 136.4) | 110.8 (89.03; 192.8) | 0.03 (-0.77; 0.83) | 0.96 | 106.5 (89.03; 175.6) | 115.2 (106.5; 192.8) | 0.18 (-0.74; 1.11) | 0.72 |
| Stim | 227.1 (192.8; 388.9) | 218.6 (201.4; 261.3) | -0.2 (-1.00; 0.6) | 0.62 | 227.1 (201.4; 227.1) | 210.0 (210.0; 261.3) | -0.08 (-1.01; 0.84) | 0.89 | |
|
VEGFR-1 (pg/mL) median (Q1;Q3) |
No stim | 6.16 (0.35; 6.16) | 6.16 (6.16; 6.16) | 0.46 (-0.35; 1.27) | 0.26 | 6.16 (6.16; 6.16) | 6.16 (6.16; 6.16) | 0.00 (-0.92; 0.92) | 1.00 |
| Stim | 24.29 (15.40; 66.24) | 94.49 (39.36; 138.4) | 0.90 (0.07; 1.74) | 0.04 | 93.28 (39.36; 138.4) | 95.70 (51.02; 138.4) | 0.08 (-0.84; 1.01) | 0.89 | |
|
PDGF-AA (pg/mL) median (Q1;Q3) |
No stim | 1.21 (0.42; 1.99) | 2.71 (1.21; 5.87) | 0.95 (0.11; 1.79) | 0.04 | 2.71 (1.22; 3.78) | 1.79 (1.21; 5.87) | -0.10 (-1.03; 0.82) | 0.86 |
| Stim | 56.54 (33.29; 62.46) | 73.97 (47.33; 96.53) | 0.77 (-0.06; 1.59) | 0.09 | 74.88 (63.92; 97.90) | 57.15 (47.33; 83.17) | -0.31 (-1.24; 0.62) | 0.54 | |
|
L-selectin (pg/mL) median (Q1;Q3) |
No stim | 1988 (1042; 1988) | 1988 (1988; 3329) | 0.46 (-0.35; 1.27) | 0.27 | 1988 (1988; 3329) | 1988 (1988; 2939) | -0.17 (-1.09; 0.76) | 0.75 |
| Stim | 2939 (1988; 2961) | 3539 (2939; 3684) | 1.34 (0.47; 2.22) | 0.007 | 3329 (2939; 3684) | 3684 (3184; 3684) | 0.19 (-0.74; 1.12) | 0.71 | |
|
MMP-8 (pg/mL) median (Q1;Q3) |
No stim | 260.4 (92.43; 274.9) | 274.9 (195.7; 328.4) | 0.68 (-0.14; 1.50) | 0.12 | 274.9 (274.9; 328.4) | 213.1 (195.7; 288.9) | -0.27 (-1.19; 0.66) | 0.59 |
| Stim | 177.2 (92.43; 229.6) | 252.9 (177.2; 274.9) | 1.00 (0.16; 1.84) | 0.04 | 260.4 (245.3; 274.9) | 229.6 (177.2; 274.9) | -0.06 (-0.99; 0.86) | 0.93 | |
|
MMP-9 (pg/mL) median (Q1;Q3) |
No stim | 111.4 (77.59; 198.1) | 56.22 (39.83; 164.7) | -0.30 (-1.11; 0.50) | 0.49 | 53.64 (39.83; 164.7) | 58.80 (46.75; 161.7) | 0.16 (-0.76; 1.09) | 0.76 |
| Stim | 260.7 (198.1; 293.9) | 345.4 (118.2; 618.1) | 0.30 (-0.51; 1.10) | 0.50 | 406.5 (323.4; 513.5) | 163.4 (118.2; 618.1) | -0.14 (-1.07; 0.78) | 0.79 | |
|
TIMP-1 (pg/mL) median (Q1;Q3) |
No stim | 19.28 (19.28; 26.57) | 62.09 (19.28; 135.4) | 0.94 (0.10; 1.78) | 0.05 | 52.86 (26.57; 95.98) | 81.82 (19.28; 135.4) | 0.02 (-0.90; 0.94) | 1.00 |
| Stim | 135.4 (128.2; 237.5) | 251.1 (194.9; 376.7) | 0.99 (0.14; 1.83) | 0.03 | 219.4 (206.0; 339.9) | 259.6 (145.2; 376.7) | 0.02 (-0.90; 0.94) | 1.00 | |
ANGPTL-6, angiopoietin-like protein 6; HC, healthy control; MMP, matrix metallopeptidase; PAH, pulmonary arterial hypertension; PDGF-AA, platelet derived growth factor AA; SSc, systemic sclerosis; stim, stimulation; TIMP-1, tissue inhibitor of metalloproteinases; VEGFR-1, vascular endothelial growth factor receptor 1.
Results are pooled from 2 independent experiments and expressed as median (first quartile; third quartile).
Effect sizes were calculated using the Cohen d. Absolute values of 0.20–0.49 represent a small change; values of 0.50–0.79 a medium change; and values of ≥ 0.80 a large change. Given the exploratory nature of this analysis, p-values were not corrected for multiplicity.