Effect of G-CSF and empagliflozin on neutrophils
| . | Control donors . | Patients . | Patients vs control donors (P values) . | Empagliflozin vs G-CSF (P values) . | Correlation with plasma 1,5-AG concentration (P values) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Under G-CSF (0) . | 3 mo . | 12 mo . | G-CSF vs control . | 3 mo vs control . | 12 mo vs control . | 3 mo vs G-CSF . | 12 mo vs G-CSF . | |||
| Number of samples | 11 | 7 | 7 | 6 | ||||||
| Sex | 6M/5F | 4M/3F | 4M/3F | 3M/3F | ||||||
| Age (y) | 14 (9-17) | 11.5 (7.5-15.5) | ||||||||
| Severe infections per y | n.d. | 3 (1.5-5) | 1 (0.5-2.5) | n.d. | .0582 | |||||
| Plasma 1,5-AG concentration (μg/mL) | n.d. | 47.2 (43.35-52.95) | 6.2 (2.85-11.2) | 5.3 (4.6-9.45) | n.d. | n.d. | n.d. | <.0001 | <.0001 | |
| Plasma G-CSF concentration (ng/mL) | 17.9 (15.8-20.8) | 135.0 (46.9-147.9) | 43.1 (23.8-72.3) | 21.4 (18.5-29.9) | <.0001 | .2546 | .9669 | .2467 | .09 | |
| Leukocytes count (×1000 cells per μL) | 6.21 (5.83-7.46) | 2.55 (2.24-4.55) | 4.4 (3.76-6.92) | 3.98 (3.62-4.34) | .0021 | .38 | .0875 | .0352 | .3783 | .0473 |
| Neutrophils count (×1000 cells per μL) | 3.10 (2.69-3,61) | 0.86 (0.58-1.18) | 1.95 (1.44-2.78) | 2.24 (2.13-2.50) | .001 | .2347 | .3247 | .0699 | .0945 | .018 |
| Lymphocytes count (×1000 cells per μL) | 2.24 (1.8-3.10) | 1.59 (1.18-2.52) | 1.83 (1.56-3.15) | 1.26 (1.12-1.83) | .2934 | .8721 | .2044 | .1034 | .7548 | .3620 |
| Monocytes count (×1000 cells per μL) | 0.56 (0.51-0.64) | 0.26 (0.21-0.44) | 0.30 (0.25-0.49) | 0.32 (0.30-0.39) | .0875 | .4193 | .6111 | .1354 | .4787 | .1945 |
| Healthy annexin-V negative (neutrophils %) | 77.0 (73.2-78.2) | 34.8 (30.9-76.3) | 61.7 (44.9-71.3) | 67.8 (57.1.1-74.6) | .0183 | .0605 | .5127 | .9597 | .5335 | .1979 |
| Apoptotic annexin-V positive (neutrophils %) | 23.0 (19.7-27.5) | 65.1 (23.5-68.5) | 38.3 (28.7-55.1) | 32.2 (25.2-42.8) | .0181 | .0567 | .4961 | .9643 | .5381 | .1915 |
| Migration (cells) | 1010 (936-1201) | 192 (124-420) | 350 (196-450) | 616 (558-653) | <.0001 | <.0001 | .0132 | .9083 | .1676 | .4290 |
| Chemotaxis response to 10 % HS (cells) | 3735 (3071-4828) | 1546 (1343-2298) | 3110 (2837-4462) | 3513 (2924-4065) | .0345 | .9977 | .9971 | .0844 | .0293 | .0457 |
| NETosis (PMA induction fold) | 4.33 (2.84-4.77) | 1.03 (0.98-1.07) | 1.16 (1.05-1.27) | 1.58 (1.41-1.80) | <.0001 | <.0001 | <.0001 | .1826 | .02 | .0007 |
| Phagocytosis of S aureus bioparticles (FU) | 3352 (2471-4440) | 1365 (774-1424) | 1809 (1342-2046) | 2470 (1904-2920) | <.0001 | .0143 | .1231 | .1656 | .028 | .0328 |
| Oxidative burst, index DHR (%) | n.d. | 0.89 (0.845-0.955) | n.d. | 0.96 (0.93-1.015) | n.d. | n.d. | n.d. | n.d. | .1292 | .1905 |
| Oxidative burst, index DHR (FMI) | n.d. | 0.97 (0.955-0.985) | n.d. | 0.94 (0.925-1.01) | n.d. | n.d. | n.d. | n.d. | .9444 | .5977 |
| cell. MPO concentration (ng/μg) | 55.3 (40.5-63.0) | 47.3 (37.2-53.0) | 43.9 (37.4-62.0) | 58.7 (46.9-61.6) | .9485 | .8253 | .9760 | .9833 | .8152 | .2521 |
| cell. LTF concentration (ng/μg) | 11.84 (10.96-13.51) | 9.52 (8.24-10.82) | 8.59 (6.06-8.92) | 8.96 (7.72-11.72) | .1982 | .0073 | .2876 | .3453 | .9954 | .7215 |
| cell. defensins concentration (ng/μg) | 44.2 (35.0-46.2) | 56.9 (42.2-72.4) | 17.15 (15.0-44.9) | 22.36 (20.72-38.69) | .2893 | .3701 | .2920 | .0451 | .0419 | .0316 |
| [plasma LTF] (ng/mL) | 0.32 (0.27-0.36) | 0.74 (0.61-0.83) | 0.19 (0.15-0.21) | 0.18 (0.10-0.34) | <.0001 | .1757 | .4234 | .0061 | .0045 | .0005 |
| Plasma defensins concentration (ng/mL) | 0.53 (0.33-0.82) | 3.06 (2.24-3.21) | 2.25 (1.46-2.31) | 1.17 (1.01-1.60) | <.0001 | .0003 | .0759 | .0098 | .0121 | .2356 |
| Plasma CAMP/LL37 concentration (ng/mL) | 7.16 (5.38-8.03) | 1.36 (0.48-3.83) | 1.04 (0.165-2.12) | 0.29 (0-1.36) | .0005 | <.0001 | <.0001 | .5726 | .4034 | .8343 |
| . | Control donors . | Patients . | Patients vs control donors (P values) . | Empagliflozin vs G-CSF (P values) . | Correlation with plasma 1,5-AG concentration (P values) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Under G-CSF (0) . | 3 mo . | 12 mo . | G-CSF vs control . | 3 mo vs control . | 12 mo vs control . | 3 mo vs G-CSF . | 12 mo vs G-CSF . | |||
| Number of samples | 11 | 7 | 7 | 6 | ||||||
| Sex | 6M/5F | 4M/3F | 4M/3F | 3M/3F | ||||||
| Age (y) | 14 (9-17) | 11.5 (7.5-15.5) | ||||||||
| Severe infections per y | n.d. | 3 (1.5-5) | 1 (0.5-2.5) | n.d. | .0582 | |||||
| Plasma 1,5-AG concentration (μg/mL) | n.d. | 47.2 (43.35-52.95) | 6.2 (2.85-11.2) | 5.3 (4.6-9.45) | n.d. | n.d. | n.d. | <.0001 | <.0001 | |
| Plasma G-CSF concentration (ng/mL) | 17.9 (15.8-20.8) | 135.0 (46.9-147.9) | 43.1 (23.8-72.3) | 21.4 (18.5-29.9) | <.0001 | .2546 | .9669 | .2467 | .09 | |
| Leukocytes count (×1000 cells per μL) | 6.21 (5.83-7.46) | 2.55 (2.24-4.55) | 4.4 (3.76-6.92) | 3.98 (3.62-4.34) | .0021 | .38 | .0875 | .0352 | .3783 | .0473 |
| Neutrophils count (×1000 cells per μL) | 3.10 (2.69-3,61) | 0.86 (0.58-1.18) | 1.95 (1.44-2.78) | 2.24 (2.13-2.50) | .001 | .2347 | .3247 | .0699 | .0945 | .018 |
| Lymphocytes count (×1000 cells per μL) | 2.24 (1.8-3.10) | 1.59 (1.18-2.52) | 1.83 (1.56-3.15) | 1.26 (1.12-1.83) | .2934 | .8721 | .2044 | .1034 | .7548 | .3620 |
| Monocytes count (×1000 cells per μL) | 0.56 (0.51-0.64) | 0.26 (0.21-0.44) | 0.30 (0.25-0.49) | 0.32 (0.30-0.39) | .0875 | .4193 | .6111 | .1354 | .4787 | .1945 |
| Healthy annexin-V negative (neutrophils %) | 77.0 (73.2-78.2) | 34.8 (30.9-76.3) | 61.7 (44.9-71.3) | 67.8 (57.1.1-74.6) | .0183 | .0605 | .5127 | .9597 | .5335 | .1979 |
| Apoptotic annexin-V positive (neutrophils %) | 23.0 (19.7-27.5) | 65.1 (23.5-68.5) | 38.3 (28.7-55.1) | 32.2 (25.2-42.8) | .0181 | .0567 | .4961 | .9643 | .5381 | .1915 |
| Migration (cells) | 1010 (936-1201) | 192 (124-420) | 350 (196-450) | 616 (558-653) | <.0001 | <.0001 | .0132 | .9083 | .1676 | .4290 |
| Chemotaxis response to 10 % HS (cells) | 3735 (3071-4828) | 1546 (1343-2298) | 3110 (2837-4462) | 3513 (2924-4065) | .0345 | .9977 | .9971 | .0844 | .0293 | .0457 |
| NETosis (PMA induction fold) | 4.33 (2.84-4.77) | 1.03 (0.98-1.07) | 1.16 (1.05-1.27) | 1.58 (1.41-1.80) | <.0001 | <.0001 | <.0001 | .1826 | .02 | .0007 |
| Phagocytosis of S aureus bioparticles (FU) | 3352 (2471-4440) | 1365 (774-1424) | 1809 (1342-2046) | 2470 (1904-2920) | <.0001 | .0143 | .1231 | .1656 | .028 | .0328 |
| Oxidative burst, index DHR (%) | n.d. | 0.89 (0.845-0.955) | n.d. | 0.96 (0.93-1.015) | n.d. | n.d. | n.d. | n.d. | .1292 | .1905 |
| Oxidative burst, index DHR (FMI) | n.d. | 0.97 (0.955-0.985) | n.d. | 0.94 (0.925-1.01) | n.d. | n.d. | n.d. | n.d. | .9444 | .5977 |
| cell. MPO concentration (ng/μg) | 55.3 (40.5-63.0) | 47.3 (37.2-53.0) | 43.9 (37.4-62.0) | 58.7 (46.9-61.6) | .9485 | .8253 | .9760 | .9833 | .8152 | .2521 |
| cell. LTF concentration (ng/μg) | 11.84 (10.96-13.51) | 9.52 (8.24-10.82) | 8.59 (6.06-8.92) | 8.96 (7.72-11.72) | .1982 | .0073 | .2876 | .3453 | .9954 | .7215 |
| cell. defensins concentration (ng/μg) | 44.2 (35.0-46.2) | 56.9 (42.2-72.4) | 17.15 (15.0-44.9) | 22.36 (20.72-38.69) | .2893 | .3701 | .2920 | .0451 | .0419 | .0316 |
| [plasma LTF] (ng/mL) | 0.32 (0.27-0.36) | 0.74 (0.61-0.83) | 0.19 (0.15-0.21) | 0.18 (0.10-0.34) | <.0001 | .1757 | .4234 | .0061 | .0045 | .0005 |
| Plasma defensins concentration (ng/mL) | 0.53 (0.33-0.82) | 3.06 (2.24-3.21) | 2.25 (1.46-2.31) | 1.17 (1.01-1.60) | <.0001 | .0003 | .0759 | .0098 | .0121 | .2356 |
| Plasma CAMP/LL37 concentration (ng/mL) | 7.16 (5.38-8.03) | 1.36 (0.48-3.83) | 1.04 (0.165-2.12) | 0.29 (0-1.36) | .0005 | <.0001 | <.0001 | .5726 | .4034 | .8343 |
Results are presented as median values with first and third quartile (Q1 and Q3). Statistically significant differences between patients and healthy controls were determined by ordinary 1-way analysis of variance for unpaired data, whereas mixed-effect analysis for paired data was used to compare values at 3 and 12 months after the start of empagliflozin treatment with values obtained before the start of treatment. The potential correlation between each parameter and plasma 1,5-AG concentration was analyzed by 2-tailed Spearman correlation assay.
Cel., intra-cellular; F, female; FI, fluoresence intensity; FMI, fluroresence mean intensity; FU, fluoresence unit; HS, human serum; M, male.