Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. ELISpot and QuantiFERON Assays
2.3. CMV Status and Viral Load
2.4. Statistics
3. Results
3.1. Correlation of Three CMV-Specific Interferon-Gamma-Release Assays
3.2. Comparison of Cellular Responses at the End of Antiviral Prophylaxis with Results One Month Thereafter
3.3. Determination of Cut-off Values for Protective T Cell Responses
3.4. Correlation of CMV-Specific Cellular Immunity with Additonal Clinical Parameters
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Recipient sex (no., %) | Male | 40 (71) |
Female | 16 (29) | |
Age, years (median, range) | 55 (20–68) | |
Disease leading to transplantation (no.) | HCV | 11 |
HBV | 9 | |
Ethyltoxic Cirrhosis | 16 | |
Autoimmune 1 | 10 | |
Other | 10 | |
Immunosuppressive regimens (no.) 2 | CNI, MMF | 44 |
CNI, mTOR | 2 | |
CNI | 4 | |
CNI, MMF, steroids | 4 | |
CNI, mTOR, steroids | 1 | |
CNI, steroids | 1 | |
CMV serostatus (no.,%) | D+/R− | 14 (25) |
D−/R+ | 17 (30) | |
D+/R+ | 25 (45) | |
Patients with CMV-DNAemia post-transplant | D+/R− | 8/14 (67) |
(no., % of the respective group) 3 | D−/R+ | 4/17 (24) |
D+/R+ | 10/25 (40) | |
Patients who received antiviral treatment for | D+/R− | 6/14 (43) |
CMV-DNAemia (no.,% of the respective group) 3 | D−/R+ | 3/17 (18) |
D+/R+ | 9/25 (36) | |
Allograft rejection (no.) | 12 |
(a) Two Different ELISpot Assays | ||||
---|---|---|---|---|
Parameter 1 | Parameter 2 | r | p | n |
IE-1 Lo (Algo) | IE OI | 0.608 | <0.0001 | 100 |
IE-1 Lo (Median) | IE OI | 0.606 | <0.0001 | 100 |
IE-1 Lo (Algo) | IE-1 Lo (Median) | 0.987 | <0.0001 | 103 |
pp65 Lo (Algo) | pp65 OI | 0.740 | <0.0001 | 99 |
pp65 Lo (Median) | pp65 OI | 0.617 | <0.0001 | 99 |
pp65 Lo (Algo) | pp65 Lo (Median) | 0.996 | <0.0001 | 103 |
IE-1 Lo (Algo) | pp65 Lo (Algo) | 0.620 | <0.0001 | 103 |
IE-1 Lo (Median) | pp65 Lo (Median) | 0.609 | <0.0001 | 103 |
IE OI | pp65 OI | 0.706 | <0.0001 | 99 |
(b) ELISpot Assays and QuantiFERON-CMV Assay | ||||
Parameter | r | p | n | |
IE-1 Lo (Algo) | 0.217 | 0.03 | 102 | |
IE-1 Lo (Median) | 0.217 | 0.03 | 102 | |
IE OI | 0.387 | <0.0001 | 99 | |
pp65 Lo (Algo) | 0.565 | <0.0001 | 102 | |
pp65 Lo (Median) | 0.551 | <0.0001 | 102 | |
pp65 OI | 0.647 | <0.0001 | 98 |
ID | Age | Sex | IE-1 | pp65 | IE-1 | pp65 | IE-1 | pp65 | IE-1 | pp65 | QuantiFERON | CMV | Start 1 | End 1 | VL | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Lo | Lo | OI | OI | Lo | Lo | OI | OI | Repli- | Max. | ||||||||||||
M0 | M0 | M0 | M0 | M1 | M1 | M1 | M1 | M0 | M1 | M2 | M3 | M4 | M5 | M6 | cation | ||||||
1 | 57 | F | 0 | 0 | 1 | 0 | 14 | 19 | 12 | 105 | 0 | 0.3 | 0 | Y | M1 | M2 | 11,172 | ||||
2 | 39 | M | 0 | 0 | 0 | 0 | n.t. | n.t. | n.t. | n.t. | 0 | 0.7 | Y | M2 | M2 | 6696 | |||||
3 | 54 | F | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 100 | 2 | Y | M3 | M4 | 2007 | |||
4 | 55 | M | 2 | 0 | 4 | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 17 | 5 | 3 | 7 | 5 | Y | M2 | M3 | 1006 |
5 | 47 | M | 0 | 0 | 0 | 0 | 1 | 7 | 20 | 40 | 0 | 0 | 7 | 4 | 100 | Y | M1 | M1 | 381 | ||
6 | 58 | F | 6 | 5 | 3 | 0 | 3 | 57 | 17 | 274 | 0 | 100 | 82 | 78 | 84 | 100 | 100 | Y | M3 | M5 | 321 |
7 | 66 | M | 0 | 1 | 0 | 2 | 1 | 100 | 4 | 76 | 0 | 38 | 4 | 4 | 0 | 8 | 7 | Y | M2 | M3 | 259 |
8 | 52 | M | 0 | 43 | 7 | 51 | 1 | 21 | 13 | 75 | 26 | 39 | 27 | 36 | 27 | Y | M1 | M1 | 258 | ||
9 | 43 | F | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N | |||
10 | 51 | M | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N | ||||
11 | 55 | M | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N | |||
12 | 26 | M | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | N | ||||
13 | 33 | M | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N | ||||||
14 | 55 | M | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N |
Test | AUC | Cohort | Time Point | Cut-Off | Sensitivity | Specificity |
---|---|---|---|---|---|---|
pp65 OI | 0.744 | All | M0 | 142 | 100% | 46% |
IE-1 Lo | 0.762 | All | M1 | 3.5 | 100% | 59% |
QuantiFERON | 0.605 | All | M1 | 32 | 100% | 23% |
pp65 Lo | 0.700 | D+/R- | M0 | 0.5 | 100% | 40% |
pp65 Lo | 0.722 | D+/R- | M1 | 0.5 | 100% | 44% |
pp65 OI | 0.722 | D+/R- | M1 | 3.5 | 100% | 44% |
QuantiFERON | 0.667 | D+/R- | M1 | 19 | 100% | 33% |
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Gliga, S.; Fiedler, M.; Dornieden, T.; Achterfeld, A.; Paul, A.; Horn, P.A.; Herzer, K.; Lindemann, M. Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients. Vaccines 2021, 9, 88. https://doi.org/10.3390/vaccines9020088
Gliga S, Fiedler M, Dornieden T, Achterfeld A, Paul A, Horn PA, Herzer K, Lindemann M. Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients. Vaccines. 2021; 9(2):88. https://doi.org/10.3390/vaccines9020088
Chicago/Turabian StyleGliga, Smaranda, Melanie Fiedler, Theresa Dornieden, Anne Achterfeld, Andreas Paul, Peter A. Horn, Kerstin Herzer, and Monika Lindemann. 2021. "Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients" Vaccines 9, no. 2: 88. https://doi.org/10.3390/vaccines9020088