CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Design and Aim
2.2. Immunosuppressive Regimens
2.3. Data Collection and Definitions
2.4. Sample Collection
2.5. Antibodies and Flow Cytometry Analysis
2.6. CD45RC+ T Cell Purification and T Cell Proliferation Analyses
2.7. Statistical Analysis
3. Results
3.1. Characteristics of the Population
3.2. Acute Rejection Episodes
3.3. Proliferative Capacities of CD45RC T Cells
3.4. Association between CD45RC Expression on T Cells and Acute Rejection
3.5. Value of CD45RC Expression on T Cell for Acute Rejection Prediction
4. Discussion
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
ABMR | antibody-mediated rejection |
AR | acute rejection |
ATG | anti-thymocytes globulins |
DSA | Donor specific anti-HLA antibodies |
HD | healthy donors |
PRA | panel reactive antibody |
PBMC | plasma blood mononuclear cells |
ROC | receiver operating curve |
TCMR | T-cell-mediated rejection |
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All Patients | |
---|---|
(n = 128) | |
Baseline Characteristics | |
Sex (M/F) | 80/48 |
Age (years) | 50.2 (18.0–79.2) |
Weigh (kg) | 71.0 (41.0–115.0) |
BMI (kg/m2) | 25.0 (17.3–40.2) |
Original nephropathy, n (%) | |
ADPKD | 33 (25.8) |
IgA nephropathy | 17 (13.3) |
Other GN | 13 (10.2) |
TIN/urologic | 13 (10.2) |
Vascular nephropathy/diabetic GN | 13 (10.2) |
Vasculitis | 3 (2.3) |
Lupus nephritis | 5 (3.9) |
Undetermined nephropathy | 18 (14.1) |
Others | 13 (10.2) |
History of transplantation | |
Pre-transplant dialysis, n (%) | 92 (71.9) |
Previous kidney transplantation, n (%) | 13 (10.2) |
Donor age, years | 50.0 (3.0–87.0) |
Cold ischemia time (hours) | 16.6 (2.0–35.4) |
HLA mismatch | |
HLA A&B&DR | 4.0 (0–6) |
HLA A&B | 3.0 (0–4) |
HLA DR | 1.0 (0–2) |
Sensitization, n (%) | |
Nonsensitized at transplantation | 89 (69.5) |
PRA < 10% | 30 (23.4) |
PRA 10–20% | 1 (0.8) |
PRA > 20% | 8 (6.2) |
Immunosuppressive regimens | |
Induction therapy | |
None, n (%) | 6 (4.7) |
Basiliximab, n (%) | 72 (56.3) |
Antithymocyte globulins, n (%) | 50 (39.1) |
Maintenance regimen | |
Tac-based, n (%) | 102 (79.6) |
Cyclosporin-based, n (%) | 26 (20.3) |
MMF or MPA, n (%) | 127 (99.2) |
Mean Follow-Up (Years) | 3.82 ± 2.22 (0.02–8.53) |
Acute Rejection | |
Number of patients, n (%) | 31 (24.2) |
Mean delay to first AR (years) | 0.73 ± 1.24 (0.02–4.83) |
Histologically proven, n (%) | 28 (90.3) |
TCMR | 24 (85.7) |
Borderline | 6 (25.0) |
Grade IA | 9 (37.5) |
Grade IB | 8 (33.3) |
Grade IIA | 1 (4.2) |
AMR | 1 (3.6) |
Mixed AR | 3 (10.7) |
Non histologically proved AR | 3 (9.7) |
More than one AR episode | 9 (7.0) |
DSA, n (%) | 15 (11.7) |
Class I | 4 (26.7) |
Class II | 11 (73.3) |
Year 1 Post-Transplant Biological Results | |
Serum creatinine (µmol/L) * | 141.4 ± 75.2 (60.0–716) |
GFR (mL/min/1.73 m2) * | 53.2 ± 21.8 (7.3–123) |
Proteinuria/Creatininuria (g/g) * | 0.25 ± 0.69 (0–5.78) |
No AR (n = 97) | AR (n = 31) | p | BPAR (n = 28) | p | Excluding Bor AR (n = 22) | p | |
---|---|---|---|---|---|---|---|
Baseline Characteristics | |||||||
Sex (M/F) | 62/35 | 18/13 | 0.558 | 16/12 | 0.514 | 12/10 | 0.413 |
Age (years) | 50.3 (18.0–79.2) | 48.2 (23.3–66.5) | 0.301 | 48.8 (23.3–66.5) | 0.368 | 45.5 (23.3–66.5) | 0.206 |
No pretransplant immunization, n (%) | 64 (66.0) | 25 (80.6) | 0.123 | 23 (82.1) | 0.160 | 18 (81.8) | 0.203 |
PRA > 20%, n (%) | 7 (7.2) | 1 (3.2) | 0.679 | 1 (3.6) | 0.682 | 1 (4.5) | 1.000 |
History of Transplantation | |||||||
Previous kidney transplantation, n (%) | 11 (11.3) | 2 (6.5) | 0.733 | 2 (7.1) | 0.731 | 2 (9.1) | 1.000 |
Pre-transplant dialysis, n (%) | 77 (72.2) | 22 (71.0) | 0.897 | 20 (71.4) | 0,939 | 15 (68.2) | 0.709 |
Donor age, years | 51.0 (3.0–87.0) | 47.0 (36.0–80.0) | 0.799 | 48 (36.0–80.0) | 0.769 | 43 (37.0–68.0) | 0.494 |
Cold ischemia time (hours) | 17.0 (2.0–35.4) | 15.6 (2.0–32.2) | 0.434 | 15.5 (2.0–32.2) | 0.299 | 15.5 (2.0–32.2) | 0.359 |
HLA mismatch (ABDR), n | 4.0 (0–6) | 4.0 (0–6) | 0.733 | 4.0 (0–6) | 0.495 | 4.0 (0–6) | 0.750 |
Delayed graft function, n (%) | 22 (22.7) | 6 (19.4) | 0.658 | 5 (17.9) | 0.551 | 4 (18.2) | 0.779 |
De novo DSA, n (%) | 12 (12.4) | 3 (9.7) | 1.000 | 3 (10.7) | 1.000 | 3 (13.6) | 1.000 |
Immunosuppressive Regimens | |||||||
Induction (none/Basiliximab/ATG), n (%) | 4 (4.1)/49 (50.5)/44 (45.4) | 2 (6.5)/23 (74.2)/6 (19.3) | 0.035 | 2(7.1)/21(75.0)/5(17.9) | 0.031 | 1(4.6)/16(72.7)/5(22.7) | 0.145 |
Tacrolimus-based regimen, n (%) | 78 (80.4) | 23 (74.2) | 0.393 | 22 (78.6) | 0.752 | 16 (72.7) | 0.370 |
Acute Rejection (all) | Yes n = 31 | No n = 97 | p |
---|---|---|---|
CD4+CD45RC high | 58.4 ± 13.7 | 51.2 ± 15.7 | 0.023 |
CD8+CD45RC high | 62.5 ± 13.3 | 53.6 ± 19.3 | 0.019 |
CD8+CD45RC int | 20.1 ± 7.7 | 23.2 ± 9.3 | 0.096 |
CD8+CD45RC low | 17.9 ± 9.8 | 23.7 ± 14.2 | 0.035 |
Biopsy-Proven AR * | Yes n = 28 | No n = 97 | p |
CD4+CD45RC high | 59.2 ± 13.3 | 51.2 ± 15.7 | 0.016 |
CD8+CD45RC high | 62.3 ± 13.0 | 53.6 ± 18.0 | 0.010 |
CD8+CD45RC int | 20.1 ± 7.9 | 23.2 ± 9.3 | 0.117 |
CD8+CD45RC low | 18.0 ± 10.3 | 23.7 ± 14.2 | 0.049 |
Acute Rejection (excluding borderline AR) ** | Yes n = 22 | No n = 97 | p |
CD4+CD45RC high | 60.0 ± 13.4 | 51.2 ± 15.7 | 0.016 |
CD8+CD45RC high | 64.4 ± 12.2 | 53.6 ± 19.3 | 0.014 |
CD8+CD45RC int | 19.7 ± 8.1 | 23.2 ± 9.3 | 0.110 |
CD8+CD45RC low | 16.4 ± 7.9 | 23.7 ± 14.2 | 0.020 |
Multivariate Cox Models | HR | 95% CI | p | |
---|---|---|---|---|
All ARs | CD8+CD45RChigh (>58.4%) | 4.04 | 1.65–9.88 | 0.002 |
Induction (ATG) | 0.39 | 0.16–0.94 | 0.037 | |
ARs excluding borderlines * | CD8+CD45RChigh (>58.4%) | 4.42 | 1.49–13.1 | 0.007 |
Induction (ATG) | 0.46 | 0.17–1.25 | 0.130 | |
Biopsy-proven ARs ** | CD8+CD45RChigh (>58.4%) | 3.59 | 1.45–8.89 | 0.006 |
Induction (ATG) | 0.35 | 0.13–0.93 | 0.035 |
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Lemerle, M.; Garnier, A.-S.; Planchais, M.; Brilland, B.; Delneste, Y.; Subra, J.-F.; Blanchet, O.; Blanchard, S.; Croue, A.; Duveau, A.; et al. CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients. J. Clin. Med. 2019, 8, 1147. https://doi.org/10.3390/jcm8081147
Lemerle M, Garnier A-S, Planchais M, Brilland B, Delneste Y, Subra J-F, Blanchet O, Blanchard S, Croue A, Duveau A, et al. CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients. Journal of Clinical Medicine. 2019; 8(8):1147. https://doi.org/10.3390/jcm8081147
Chicago/Turabian StyleLemerle, Marie, Anne-Sophie Garnier, Martin Planchais, Benoit Brilland, Yves Delneste, Jean-François Subra, Odile Blanchet, Simon Blanchard, Anne Croue, Agnès Duveau, and et al. 2019. "CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients" Journal of Clinical Medicine 8, no. 8: 1147. https://doi.org/10.3390/jcm8081147