Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease
Abstract
:1. Introduction
2. Results
2.1. Participant Demographics
2.2. Variability in Measures Related to Oxidative Stress
2.3. Variability in Measures Related to Inflammation
3. Discussion
4. Materials and Methods
4.1. Study Participants
4.2. Blood Sample Collection
- (1)
- Intracellular glutathione (GSH) status measured as total GSH and the redox ratio of reduced/oxidized glutathione (GSH/GSSG) in RBCs;
- (2)
- The activity of intracellular antioxidant enzymes-catalase (CAT), superoxide dismutase (SOD), and Glutathione peroxidase (GPx) in RBCs;
- (3)
- Plasma lipid peroxidation profile as determined by malondialdehyde (MDA) levels;
- (4)
- Oxidative modification of proteins determined as protein carbonylation (Protein carbonyl) levels in plasma.
- (1)
- Pro-inflammation cytokines: interleukin-1 receptor antagonist (IL-1RA), interleukins (IL-6, IL-8, IL-10), tumor necrosis factor-alpha (TNFa), monocyte chemoattractant protein-1 (MCP-1) measured in plasma;
- (2)
- Inflammation markers related to skeletal manifestations: macrophage inflammatory protein (MIP)-1alpha (MIP-1a) and MIP-1beta (MIP-1b), measured in plasma.
4.3. Measurement of Oxidative Stress
4.4. Measurement of Inflammation
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Healthy Control (N = 18) | Gaucher Disease Type 1 (GD1) | |
---|---|---|---|
GD-Naïve (N = 5) | GD-Treated (N = 13) | ||
Female | 9 (50%) | 3 (60.0%) | 8 (61.5%) |
Caucasian | 12 (75.0%) | 5 (100%) | 12 (92.3%) |
Age (in years) | 40.8 (15.3) | 60.0 (9.3) | 46.9 (12.0) |
GD1 biomarkers | |||
CHITO (nmoles/h/mL) | <78.5 * | 3590 (4182.5) 1 | 220 (224.2) 7 |
ACE (IU/L) | 32.8–107.9 * | 95.6 (86.7) 2 | 62.8 (35.2) 5 |
TRAP (IU/L) | 0.28–9.84 * | 25.2 (11.7) 3 | 7.18 (2.6) 8 |
Complete blood count | |||
Hemoglobin (g/L) | ND | 13.6 (1.7) | 14.4 (1.7) 2 |
Hematocrit (%) | 39.4 (5.6) 1 | 42.3 (4.9) 2 | |
Neutrophil (%) | 72.5 (0.7) 3 | 55.2 (7.4) 6 | |
Lymphocyte (%) | 23.3 (9.2) 2 | 34.0 (6.8) 5 | |
Eosinophils (%) | 1.5 (0.7) 3 | 2.83 (3.4) 6 | |
WBC (×109/L) | 5.62 (1.0) | 6.02 (2.5) 3 | |
Platelets (×109/L) | 122 (28.1) | 189 (65.5) 3 | |
Mutational status | |||
N370S/N370S | NA | 4 (80%) | 5 (38.5%) |
N370S/L444P | 5 (38.5%) | ||
N370S/unknown | 1 (7.7%) | ||
N370S/R463C | 1 (7.7%) | ||
Unknown | 1 (20%) | 1 (7.7%) | |
GD1 therapy | |||
Years on therapy | NA | NA | 16.1 (8.3) |
ERT | NA | 6 (46.1%) | |
SRT | NA | 7 (53.8%) |
Biomarker | %CV Overall | %CV Healthy Control | %CV GD-Naïve | %CV GD-Treated |
---|---|---|---|---|
Total GSH | 25.5 | 23.2 | 17.2 | 23.6 |
Ratio GSH/GSSG | 82.6 | 58.6 | 16.7 | 86.7 |
CAT Activity | 74.0 | 65.9 | 17.4 | 38.4 |
SOD Activity | 55.7 | 66.4 | 29.7 | 42.7 |
GPx Activity | 33.3 | 32.2 | 31.9 | 30.9 |
Protein Carbonyl | 162.3 | 143.9 | 104.7 | 63.6 |
MDA | 51.1 | 46.3 | 25.6 | 42.6 |
IL1RA | 81.5 | 41.6 | 38.0 | 66.0 |
IL-6 | 60.4 | 69.8 | 39.3 | 56.5 |
IL-8 | 76.3 | 38.1 | 36.5 | 82.2 |
MCP1 | 51.0 | 50.6 | 36.7 | 54.1 |
MIP-1a | 164.7 | 81.3 | 205.9 | 173.1 |
MIP-1b | 138.1 | 87.5 | 60.9 | 84.0 |
TNFa | 85.9 | 113.7 | 52.7 | 67.1 |
IL-10 | 701.6 * | 129.4 | 138.5 | 484.4 * |
Biomarker | Healthy Control | GD-Naïve | GD-Treated |
---|---|---|---|
N = 18 | N = 5 | N = 13 | |
Total_GSH (µg/mL) | |||
Mean (SD) | 620 (144) | 516 (89) | 483 (114) |
Median (IQR) | 614 (189) | 509 (122) | 439 (163) |
Unknown | 6 | 0 | 2 |
Ratio_GSHGSSG | |||
Mean (SD) | 29 (17) | 6 (1) | 15 (13) |
Median (IQR) | 27 (28) | 6 (2) | 10 (15) |
Unknown | 5 | 0 | 2 |
CAT_Activity (nmol/min/mL/mg) | |||
Mean (SD) | 563 (371) | 321 (56) | 245 (94) |
Median (IQR) | 388 (534) | 326 (71) | 244 (126) |
Unknown | 4 | 0 | 2 |
SOD_Activity (U/mL/mg) | |||
Mean (SD) | 6.01 (3.99) | 4.71 (1.40) | 6.18 (2.64) |
Median (IQR) | 4.95 (2.69) | 4.43 (1.36) | 5.68 (4.11) |
Unknown | 4 | 0 | 2 |
GPx_Activity (nmol/min/mL/mg) | |||
Mean (SD) | 18.0 (5.8) | 14.1 (4.5) | 15.2 (4.7) |
Median (IQR) | 19.2 (7.8) | 14.4 (5.7) | 15.0 (5.4) |
Unknown | 4 | 0 | 2 |
Protein_Carbonyl (nmol/mg) | |||
Mean (SD) | 1.55 (2.23) | 0.43 (0.45) | 0.55 (0.35) |
Median (IQR) | 0.64 (0.80) | 0.27 (0.33) | 0.54 (0.39) |
Unknown | 4 | 0 | 1 |
MDA (nM/mg) | |||
Mean (SD) | 41 (19) | 90 (23) | 68 (29) |
Median (IQR) | 38 (23) | 88 (17) | 65 (45) |
Unknown | 4 | 1 | 1 |
IL1RA (pg/mL) | |||
Mean (SD) | 255 (106) | 1043 (396) | 694 (458) |
Median (IQR) | 256 (155) | 1000 (513) | 619 (540) |
Unknown | 5 | 0 | 1 |
IL-6 (pg/mL) | |||
Mean (SD) | 1.82 (1.27) | 2.14 (0.84) | 2.30 (1.30) |
Median (IQR) | 2.29 (2.25) | 2.08 (0.95) | 2.26 (1.53) |
Unknown | 5 | 0 | 1 |
IL-8 (pg/mL) | |||
Mean (SD) | 2.52 (0.96) | 6.94 (2.53) | 4.65 (3.82) |
Median (IQR) | 2.56 (0.90) | 7.05 (2.35) | 3.13 (2.52) |
Unknown | 5 | 0 | 1 |
MCP1 (pg/mL) | |||
Mean (SD) | 81 (41) | 90 (33) | 98 (53) |
Median (IQR) | 68 (43) | 89 (32) | 78 (62) |
Minimum–Maximum | 32–219 | 31–139 | 45–304 |
Unknown | 5 | 0 | 1 |
MIP-1a (pg/mL) | |||
Mean (SD) | 16 (13) | 17 (35) | 26 (45) |
Median (IQR) | 15 (22) | 0 (0) | 1 (36) |
Minimum–Maximum | 0–43 | 0–102 | 0–194 |
Unknown | 5 | 0 | 1 |
MIP-1b (pg/mL) | |||
Mean (SD) | 8 (7) | 87 (53) | 25 (21) |
Median (IQR) | 7 (11) | 71 (51) | 22 (22) |
Unknown | 5 | 0 | 1 |
TNFa (pg/mL) | |||
Mean (SD) | 0.73 (0.83) | 1.86 (0.98) | 1.40 (0.94) |
Median (IQR) | 0.27 (1.27) | 1.84 (1.33) | 1.58 (1.35) |
Unknown | 5 | 0 | 1 |
IL-10 (U/mL) | |||
Mean (SD) | 0.34 (0.44) | 0.39 (0.54) | 4.42 (21.41) * |
Median (IQR) | 0.08 (0.91) | 0.08 (1.00) | 1.02 (1.17) * |
Unknown | 5 | 0 | 1 |
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Sahasrabudhe, S.A.; Terluk, M.R.; Rudser, K.D.; Cloyd, J.C.; Kartha, R.V. Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease. Int. J. Mol. Sci. 2022, 23, 9189. https://doi.org/10.3390/ijms23169189
Sahasrabudhe SA, Terluk MR, Rudser KD, Cloyd JC, Kartha RV. Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease. International Journal of Molecular Sciences. 2022; 23(16):9189. https://doi.org/10.3390/ijms23169189
Chicago/Turabian StyleSahasrabudhe, Siddhee A., Marcia R. Terluk, Kyle D. Rudser, James C. Cloyd, and Reena V. Kartha. 2022. "Biological Variation in Peripheral Inflammation and Oxidative Stress Biomarkers in Individuals with Gaucher Disease" International Journal of Molecular Sciences 23, no. 16: 9189. https://doi.org/10.3390/ijms23169189