A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome
Abstract
:1. Introduction
2. Results
2.1. Patients
2.2. Principal Component Analysis Using Gene Transcripts
2.3. Rejection-Associated Gene Score (RAG Score)
2.4. RAG Score and Outcome
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Biopsies
4.3. RNA Extraction and Microarray Hybridization
4.4. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
IFTA | Interstitial fibrosis and tubular atrophy |
BL-C | Borderline changes in biopsies for cause |
BL-S | Borderline changes in surveillance biopsies |
IFTA-C | Interstitial fibrosis and tubular atrophy in biopsies for cause |
IFTA-S | Interstitial fibrosis and tubular atrophy in surveillance biopsies |
REJ-C | Rejection in biopsies for cause |
REJ-S | Rejection in surveillance biopsies |
RAG | Rejection-associated gene score |
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Available Biopsies | Included Biopsies | |||
---|---|---|---|---|
For Cause | Surveillance | For Cause | Surveillance | |
Normal | 0 | 39 | 0 | 17 |
Borderline changes | 19 | 18 | 13 | 12 |
IFTA | 35 | 32 | 20 | 16 |
TCMR | 6 | 5 | 6 a | 5 c |
ABMR | 6 | 1 | 6 b | 1 d |
Total | 66 | 95 | 45 | 51 |
Variable | Normal | REJ-C | REJ-S | BL-C | BL-S | IFTA-C | IFTA-S | p-Value |
---|---|---|---|---|---|---|---|---|
N | 17 | 12 | 6 | 13 | 12 | 20 | 16 | |
Age (y) | 54 ± 13 | 43 ± 12 | 53 ± 21 | 59 ± 11 b | 57 ± 13 b,c | 46 ± 15 c | 52 ± 17 | 0.060 |
Sex (m/f) | 12/5 | 6/6 | 4/2 | 8/5 | 9/3 | 16/4 | 10/6 | 0.610 |
1st Tx/Re-Tx | 17/0 | 8/4 | 6/0 | 13/0 | 12/0 | 18/2 | 12/4 | 0.002 |
Donor age (y) | 56 ± 15 | 44 ± 16 | 59 ± 15 | 59 ± 14 | 53 ± 16 | 58 ± 11 | 57 ± 16 | 0.226 |
HLA (A + B + DR) mm | 3.8 ± 1.0 | 3.7 ± 1.4 | 4.0 ± 1.9 | 3.9 ± 1.0 | 3.8 ± 0.7 | 3.5 ± 1.3 | 3.7 ± 1.1 | 0.942 |
DGF (no/yes) | 15/2 | 10/1 | 6/0 | 5/8 | 10/2 | 14/1 | 13/3 | 0.010 |
Rejection (no/yes) | 17/0 | 8/4 | 4/2 | 12/1 | 9/3 | 19/1 | 14/2 | 0.082 |
Induction (ATG/IL2RAb) | 4/13 | 7/5 | 2/4 | 4/15 | 7/9 | 4/14 | 7/9 | 0.295 |
Immunosuppression TAC + MMF + S/other | 16/1 | 10/2 | 4/2 | 9/4 | 12/0 | 14/6 | 16/0 | 0.036 |
Time biopsy (m) | 6 ± 5 | 51 ± 57 a | 6 ± 6 b | 25 ± 27 | 7 ± 4 b,d | 77 ± 78 a,c,e | 7 ± 5 b,f | <0.001 |
Creatinine (mg/dL) | 1.3 ± 0.3 | 2.0 ± 0.6 a | 1.4 ± 0.2 | 2.5 ± 0.8 a,b,c | 1.3 ± 0.3 b,d | 2.1 ± 0.7 a,c,e | 1.4 ± 0.3 b,d,f | <0.001 |
UPCR (g/g) | 0.4 ± 0.3 | 1.7 ± 1.5 a | 0.3 ± 0.1 b | 1.1 ± 1.2 a,b,c | 0.3 ± 0.2 b,d | 1.3 ± 0.9 a,c,e | 0.3 ± 0.3 b,d,f | <0.001 |
DSA (no/yes) | 17/0 | 8/4 | 5/1 | 13/0 | 12/0 | 20/0 | 16/0 | <0.001 |
Variable | Normal | REJ-C | REJ-S | BL-C | BL-S | IFTA-C | IFTA-S |
---|---|---|---|---|---|---|---|
N | 17 | 12 | 6 | 13 | 12 | 20 | 16 |
Glomeruli (N) | 16 ± 8 | 16 ± 6 | 17 ± 5 | 17 ± 6 | 21 ± 11 | 17 ± 8 | 23 ± 12 |
Gs (%) | 7 ± 7 | 22 ± 23 | 12 ± 16 | 22 ± 15 | 12 ± 14 | 31 ± 24 | 10 ± 6 |
g | 0.1 ± 0.3 | 1.4 ± 1.1 | 0.8 ± 1.3 | 0.2 ± 0.4 | 0.4 ± 0.8 | 0.3 ± 0.6 | 0.2 ± 0.4 |
i | 0.1 ± 0.2 | 1.3 ± 1.1 | 1.5 ± 0.5 | 1.2 ± 0.7 | 0.7 ± 0.6 | 0.1 ± 0.3 | 0.1 ± 0.2 |
t | 0 | 1.2 ± 0.9 | 1.8 ± 0.7 | 1.0 ± 0 | 1.0 ± 0.6 | 0.2 ± 0.4 | 0.1 ± 0.3 |
v | 0 | 0.3 ± 0.6 | 0.5 ± 0.5 | 0 | 0 | 0 | 0 |
ah | 0.2 ± 0.4 | 1.4 ± 1.2 | 0 | 1.0 ± 0.9 | 0.7 ± 0.-6 | 1.3 ± 1.2 | 0.6 ± 0.6 |
cg | 0 | 0.7 ± 0.9 | 0 | 0 | 0.2 ± 0.6 | 0.2 ± 0.5 | 0 |
ci | 0.1 ± 0.3 | 1.2 ± 0.9 | 0.8 ± 1.0 | 1.3 ± 0.6 | 0.9 ± 0.8 | 1.8 ± 0.8 | 1.3 ± 0.5 |
ct | 0.6 ± 0.5 | 1.1 ± 0.8 | 1.0 ± 0.6 | 1.2 ± 0.4 | 1.0 ± 0.4 | 1.6 ± 0.9 | 1.1 ± 0.3 |
cv | 0.4 ± 0.7 | 0.8 ± 0.8 | 0.3 ± 0.5 | 1.0 ± 0.8 | 0.4 ± 0.5 | 1.3 ± 1.2 | 0.9 ± 0.8 |
mm | 0.1 ± 0.2 | 0.5 ± 0.7 | 0 | 0.1 ± 0.3 | 0 | 0.2 ± 0.7 | 0 |
ptc | 0.1 ± 0.2 | 1.4 ± 0.8 | 0.7 ± 1.2 | 0.6 ± 0.8 | 0.4 ± 0.8 | 0.5 ± 0.8 | 0.1 ± 0.2 |
C4d | 0 | 0.3 ± 0.5 | 0 | 0 | 0 | 0 | 0 |
i-IFTA | 0.4 ± 0.9 | 2.1 ± 1.3 | 2.2 ± 1.3 | 2.1 ± 0.8 | 1.3 ± 1.1 | 2.2 ± 1.0 | 1.8 ± 0.9 |
t-IFTA | 0.2 ± 0.4 | 0.9 ± 0.6 | 0.8 ± 0.4 | 0.7 ± 0.7 | 0.6 ± 0.7 | 0.7 ± 0.6 | 0.7 ± 0.5 |
i-total | 0.1 ± 0.2 | 1.3 ± 0.6 | 1.7 ± 0.6 | 1.5 ± 0.7 | 0.8 ± 0.6 | 0.7 ± 0.5 | 0.4 ± 0.3 |
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Chamoun, B.; Caraben, A.; Torres, I.B.; Sellares, J.; Jiménez, R.; Toapanta, N.; Cidraque, I.; Gabaldon, A.; Perelló, M.; Gonzalo, R.; et al. A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome. Int. J. Mol. Sci. 2020, 21, 8237. https://doi.org/10.3390/ijms21218237
Chamoun B, Caraben A, Torres IB, Sellares J, Jiménez R, Toapanta N, Cidraque I, Gabaldon A, Perelló M, Gonzalo R, et al. A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome. International Journal of Molecular Sciences. 2020; 21(21):8237. https://doi.org/10.3390/ijms21218237
Chicago/Turabian StyleChamoun, Betty, Anna Caraben, Irina B. Torres, Joana Sellares, Raquel Jiménez, Néstor Toapanta, Ignacio Cidraque, Alejandra Gabaldon, Manel Perelló, Ricardo Gonzalo, and et al. 2020. "A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome" International Journal of Molecular Sciences 21, no. 21: 8237. https://doi.org/10.3390/ijms21218237