Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles
Abstract
1. Introduction
2. Results
2.1. Demographic Characteristics of the Study Population
2.2. Histopathological Characteristics of Renal Allograft Biopsies
2.3. Plasma MMP-1, MMP-2, and MMP-3 Levels in Patients with Antibody-Mediated Rejection (ABMR)
2.4. Plasma Concentrations of MMP-1, MMP-2, MMP-3, TIMP-3 Can Predict ABMR
2.5. Correlation of MMPs and TIMPs Concentrations with the Severity of Histopathological Findings
3. Discussion
4. Materials and Methods
4.1. Clinical Parameters
4.2. Clinical-Pathological Diagnosis
4.3. Measurement of Circulating Anti-HLA Antibodies
4.4. Determination of MMPs and TIMPs Concentrations
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABMR | Acute Antibody-Mediated Rejection |
AUC | Area Under the Curve |
BMI | Body Mass Index |
BSA | Bovine Serum Albumin |
CDC-XM | Complement-Dependent Cytotoxicity Crossmatch |
CF-XM | Flow Cytometry Crossmatch |
CI | Confidence Interval |
C4d | C4d deposition in peritubular capillaries |
Cg | Chronic Glomerulopathy |
Ci | Interstitial Fibrosis |
Ct | Tubular Atrophy |
Cv | Vascular fibrous intimal thickening |
DNDSA | De Novo Donor-Specific Antibodies |
DSA | Donor-Specific Antibodies |
ECM | Extracellular Matrix |
EDTA | Ethylenediaminetetraacetic Acid |
EGFR | Estimated Glomerular Filtration Rate |
ELISA | Enzyme-Linked Immunosorbent Assay |
EMT | Epithelial–Mesenchymal Transition |
G | Glomerulitis |
HLA | Human Leukocyte Antigen |
HRP | Horseradish Peroxidase |
I | Interstitial inflammation |
i-IFTA | Inflammation in areas of interstitial fibrosis and tubular atrophy |
IL-1β | Interleukin-1 Beta |
IQR | Interquartile Range |
MFI | Mean Fluorescence Intensity |
MGN | Membranous Glomerulonephritis |
MMP | Matrix Metalloproteinase |
MM | Mesangial Matrix Expansion |
NR | No-Rejection |
OR | Odds Ratio |
PBS | Phosphate-Buffered Saline |
PPV | Positive Predictive Value |
PRA-SA | Panel Reactive Antibody by Solid Assay |
PTC | Peritubular Capillaritis |
Rho | Spearman’s Rho |
ROC | Receiver Operating Characteristic |
SPSS | Statistical Package for the Social Sciences |
T | Tubulitis |
TGF-β | Transforming Growth Factor Beta |
TIMP | Tissue Inhibitor of Metalloproteinases |
TMB | Tetramethylbenzidine |
TNF-α | Tumor Necrosis Factor Alpha |
V | Intimal arteritis |
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Total (n = 27) | NR (n = 12) | ABMR (n = 15) | p Value | |
---|---|---|---|---|
Female | 14 (51.9) | 8 (66.7) | 6 (40) | 0.16 |
Age | 42 (32–51) | 51 (37–59) | 34 (31–42) | 0.03 |
BMI (kg/m2) | 26.10 (21.90–29.30) | 25.75 (21.85–29.85) | 26.1 (21.95–28.2) | 0.94 |
Etiology | 0.12 | |||
Unknown | 16 (59.3) | 4 (41.6) | 11 (73.3) | |
MGN | 9 (33.3) | 5 (41.7) | 4 (26.7) | |
Diabetes | 2 (7.4) | 2 (16.7) | 0 | |
Time post-transplantation (months) | 80.5 (16–112) | 37.8 (10.2–102) | 85 (37.5–112) | 0.22 |
Deceased donor | 13 (48.2) | 7 (58.3) | 6 (40) | 0.29 |
Allosensitization | 17 (63) | 6 (50) | 11 (73.3) | 0.2 |
PRA I | 1 (0–5) | 1 (0–2) | 3 (0–10) | 0.34 |
PRA II | 2 (1–6) | 2 (0.5–6) | 2 (1–44) | 0.57 |
DSAs pre-transplantation | 9(33.3) | 2 (16.7) | 7 (46.7) | 0.15 |
DSAs post-transplantation | 20 (74.1) | 6 (50) | 15 (100) | 0.003 |
Total (n = 27) | NR (n = 12) | ABMR (n = 15) | p-Value | |
---|---|---|---|---|
g > 0 | 22 (81.5) | 7 (58.3) | 15 (100) | 0.01 |
ptc > 0 | 16 (59.3) | 1 (8.3) | 15 (100) | <0.001 |
mm > 0 | 22 (81.5) | 7 (58.3) | 15 (100) | 0.01 |
i > 0 | 9 (33.3) | 0 | 9 (60) | 0.001 |
t > 0 | 9 (33.3) | 1 (8.3) | 8 (53.3) | 0.02 |
v > 0 | 3 (11.1) | 0 | 3 (20) | 0.16 |
cg > 0 | 6 (22.2) | 0 | 6 (40) | 0.02 |
ci > 0 | 22 (81.5) | 9 (75) | 13 (86.7) | 0.39 |
ct > 0 | 22 (81.5) | 9 (75) | 13 (86.7) | 0.39 |
cv > 0 | 11 (40.7) | 3 (25) | 8 (53.3) | 0.14 |
i-IFTA > 0 | 14 (52.9) | 5 (41.7) | 9 (60) | 0.29 |
C4d > 0 | 9 (33.3) | 5 (41.7) | 4 (26.7) | 0.34 |
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Vázquez-Toledo, M.A.; Sánchez-Muñoz, F.; Zepeda-Quiroz, I.; Guzmán-Martín, C.A.; Osorio-Alonso, H.; Daniel, J.-V.; Soto-Abraham, M.V.; Moguel-González, B.; Chacón-Salinas, R.; Flores-Gama, C.; et al. Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. Int. J. Mol. Sci. 2025, 26, 6011. https://doi.org/10.3390/ijms26136011
Vázquez-Toledo MA, Sánchez-Muñoz F, Zepeda-Quiroz I, Guzmán-Martín CA, Osorio-Alonso H, Daniel J-V, Soto-Abraham MV, Moguel-González B, Chacón-Salinas R, Flores-Gama C, et al. Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. International Journal of Molecular Sciences. 2025; 26(13):6011. https://doi.org/10.3390/ijms26136011
Chicago/Turabian StyleVázquez-Toledo, Miguel A., Fausto Sánchez-Muñoz, Iván Zepeda-Quiroz, Carlos A. Guzmán-Martín, Horacio Osorio-Alonso, Juárez-Villa Daniel, Ma. Virgilia Soto-Abraham, Bernardo Moguel-González, Rommel Chacón-Salinas, César Flores-Gama, and et al. 2025. "Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles" International Journal of Molecular Sciences 26, no. 13: 6011. https://doi.org/10.3390/ijms26136011
APA StyleVázquez-Toledo, M. A., Sánchez-Muñoz, F., Zepeda-Quiroz, I., Guzmán-Martín, C. A., Osorio-Alonso, H., Daniel, J.-V., Soto-Abraham, M. V., Moguel-González, B., Chacón-Salinas, R., Flores-Gama, C., & Springall, R. (2025). Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles. International Journal of Molecular Sciences, 26(13), 6011. https://doi.org/10.3390/ijms26136011