HLA-E Polymorphism Determines Susceptibility to BK Virus Nephropathy after Living-Donor Kidney Transplant
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population, BKPyV and PyVAN Screening
2.2. HLA-E Genotyping
2.3. Prediction of HLA-E Affinity for BKPyV Derived Peptides
2.4. Statistical Analysis
3. Results
3.1. HLA-E*01:01 May Be Able to Present Peptide Sequences Derived from BKPyV
3.2. HLA-E*01:01 Homozygosity Exerts Protection against PyVAN
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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A | B | C | ||
---|---|---|---|---|
Total | HLA-E*01:03 Carrier# | HLA-E*01:03 Non-Carrier | p-Value B vs. C | |
Donor | N = 278 | N = 211 | N = 67 | |
Sex (men/women) | 115/163 | 89/122 | 26/41 | 0.67 a |
Age (y) ±SD | 51.41 ± 10.03 | 51.99 ± 10.06 | 43.30 ± 9.83 | 0.10 b |
Recipient | N = 278 | N = 198 | N = 80 | |
Sex (men/women) | 162/116 | 116/82 | 46/34 | 0.87 a |
Age (y) ±SD | 41.06 ± 15.43 | 40.46 ± 15.42 | 42.53 ± 15.47 | 0.32 b |
KTx Related Variables | ||||
HLA A, B mismatches, mean ± SD | 1.97 ± 1.14 | 1.83 ± 1.1 | 2.31 ± 1.17 | 0.002 **b |
HLA-DR mismatch, mean ± SD | 1.12 ± 0.62 | 1.09 ± 0.60 | 1.19 ± 0.66 | 0.22 b |
Panel of Antibodies (%) | ||||
0% | 244 | 172 | 72 | 0.55 a |
1–10% | 14 | 9 | 5 | 0.55 a |
10–50% | 14 | 12 | 2 | 0.36 a |
>50% | 6 | 5 | 1 | 0.68 a |
Cold ischemia time, median, in minutes (range) | 134.99 ± 48.90 | 136.07 ± 48.63 | 131.32 ± 48.86 | 0.57 b |
Warm ischemia time, median, in minutes (range) | 19.97 ± 6.87 | 19.38 ± 5.84 | 21.46 ± 8.83 | 0.057 b |
Immunosuppressive Therapy | ||||
ATG-based induction therapy, yes/no | 13/265 | 9/189 | 4/76 | 1 a |
CNI administration, yes/no | 278/0 | 198/0 | 80/0 | nd |
MMF co-administration, yes/no | 260/18 | 189/9 | 75/5 | 0.55 a |
Steroid co-administration, yes/no | 278/0 | 198/0 | 80/0 | nd |
PyVAN and CMV | ||||
PyVAN, yes/no | 11/267 | 11/187 | 0/80 | 0.031 *a |
CMV positive recipient | 159/119 | 116/82 | 43/37 | 0.46 a |
CMV positive donor | 177/101 | 128/70 | 49/31 | 0.59 a |
CMV Infection, yes/no | 38/240 | 32/166 | 6/74 | 0.057 a |
PyVAN and CMV infection, yes/no | 3/275 | 3/195 | 0/80 | 0.27 a |
PyVAN or CMV infection vs. no PyVAN and no CMV infection | 46/232 | 40/158 | 6/74 | 0.01 a |
Large-T and Small-t Antigen | |||
---|---|---|---|
Position | Peptide | 1 − log50k(aff) | Affinity (nM) |
416 | NVPKRRYWL | 0.202 | 5619.93 |
568 | RILQSGMTL | 0.173 | 7666.40 |
454 | PMERLTFEL | 0.165 | 8432.78 |
557 | SLQNSEFLL | 0.160 | 8874.14 |
570 | LQSGMTLLL | 0.150 | 9850.58 |
BK Polyomavirus Major Capsid Protein VP1 | |||
---|---|---|---|
Position | Peptide | 1 − log50k(aff) | Affinity (nM) |
18 | KEPVQVPKL | 0.186 | 6716.19 |
237 | TNTATTVLL | 0.142 | 10,773.00 |
297 | NPYPISFLL | 0.139 | 11,067.54 |
BK Polyomavirus Major Capsid Protein VP2 | |||
---|---|---|---|
Position | Peptide | 1 − log50k(aff) | Affinity(nM) |
292 | WMLPLLLGL | 0.152 | 9685.81 |
BK polyomavirus agnoprotein | |||
---|---|---|---|
Position | Peptide | 1 − log50k(aff) | Affinity (nM) |
46 | SXXPESVMF | 0.139 | 11,081.08 |
52 | VMFCEPKNL | 0.139 | 11,162.18 |
Derived from | Peptide | 1 − log50k(aff) | Affinity (nM) |
---|---|---|---|
Human leukocyte antigen-Cw*3 | VMAPRTLIL | 0.589 | 85.69 |
CMV protein pUL40 | VMAPRTLIL | 0.589 | 85.69 |
Human leukocyte antigen-G | VMAPRTLFL | 0.564 | 112.12 |
Mycobacterium tuberculosis enoyl-[acyl-carrier-protein] reductase [NADH] | RLPAKAPLL | 0.547 | 134.77 |
CMV phosphorylated matrix protein pp65 (UL83) | VLPHETRLL | 0.330 | 1405.23 |
CMV immediate-early protein 1 (pUL123) | VMLAKRPLI | 0.303 | 1887.52 |
Human heat shock protein 60 (hsp60) | QMRPVSRVL | 0.276 | 2530.17 |
CMV protein pUL18 | SEPQCNPLL | 0.273 | 2614.63 |
BK polyomavirus large-T and small-t antigen | NVPKRRYWL | 0.202 | 5619.93 |
BK polyomavirus major capsid protein VP1 | KEPVQVPKL | 0.186 | 6716.19 |
Human immunodeficiency virus 1 Gag protein | RMYSPVSIL | 0.173 | 7728.11 |
BK polyomavirus major capsid protein VP2 | WMLPLLLGL | 0.152 | 9685.81 |
BK polyomavirus agnoprotein | SXXPESVMF | 0.139 | 11081.08 |
(A) Recipient HLA-E genotype | PyVAN N = 11 | No PyVAN N = 267 | p-Value | OR | 95% CI |
01:03/01:03 | 3 (27.3%) | 61 (22.8%) | 0.73 | 1.26 | 0.33–4.92 |
01:01/01:03 | 8 (72.7%) | 126 (47.2%) | 0.10 | 2.98 | 0.77–11.50 |
01:01/01:01 | 0 (0%) | 80 (30%) | 0.025 * | 0.09 | 0.005–1.59 |
Allele Frequencies | |||||
01:03 | 14 | 248 | 0.11 | 2.02 | 0.83–4.89 |
01:01 | 8 | 286 | |||
(B) Donor HLA-E genotype | PyVAN N = 11 | No PyVAN N = 267 | p-Value | OR | CI (95%) |
01:03/01:03 | 1 (9.1%) | 62 (23.2%) | 0.27 | 0.33 | 0.04–2.63 |
01:01/01:03 | 9 (81.8%) | 139 (52.1%) | 0.052 | 4.14 | 0.89–19.55 |
01:01/01:01 | 1 (9.1%) | 66 (24.7%) | 0.24 | 0.3 | 0.04–2.42 |
Allele Frequencies | |||||
01:03 | 11 | 263 | 0.77 | 1.1 | 0.47–2.7 |
01:01 | 10 | 271 |
(A) Recipient HLA-E genotype | PyVAN or CMV Infection N = 46 | No PyVAN and no CMV Infection N = 267 | p-Value | OR | 95% CI |
01:03/01:03 | 12 (26.1%) | 52 (22.4%) | 0.57 | 1.22 | 0.59–2.53 |
01:01/01:03 | 28 (60.9%) | 106 (45.7%) | 0.07 | 1.85 | 0.96–3.53 |
01:01/01:01 | 6 (13.0%) | 74 (31.9%) | 0.012 * | 0.32 | 0.13–0.79 |
Allele Frequencies | |||||
01:03 | 52 | 210 | 0.052 | 1.57 | 1.00–2.47 |
01:01 | 40 | 254 | |||
(B) Donor HLA-E genotype | PyVAN or CMV Infection N = 46 | No PyVAN and no CMV Infection N = 267 | p-Value | OR | CI (95%) |
01:03/01:03 | 12 (9.1%) | 51 (22.0%) | 0.44 | 1.33 | 0.64–2.79 |
01:01/01:03 | 26 (81.8%) | 122 (52.6%) | 0.75 | 1.17 | 0.62–2.22 |
01:01/01:01 | 8 (9.1%) | 59 (25.4%) | 0.34 | 0.62 | 0.27–1.39 |
Allele Frequencies | |||||
01:03 | 50 | 224 | 0.31 | 1.3 | 0.81–1.99 |
01:01 | 42 | 240 |
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Rohn, H.; Michita, R.T.; Schramm, S.; Dolff, S.; Gäckler, A.; Korth, J.; Heinemann, F.M.; Wilde, B.; Trilling, M.; Horn, P.A.; et al. HLA-E Polymorphism Determines Susceptibility to BK Virus Nephropathy after Living-Donor Kidney Transplant. Cells 2019, 8, 847. https://doi.org/10.3390/cells8080847
Rohn H, Michita RT, Schramm S, Dolff S, Gäckler A, Korth J, Heinemann FM, Wilde B, Trilling M, Horn PA, et al. HLA-E Polymorphism Determines Susceptibility to BK Virus Nephropathy after Living-Donor Kidney Transplant. Cells. 2019; 8(8):847. https://doi.org/10.3390/cells8080847
Chicago/Turabian StyleRohn, Hana, Rafael Tomoya Michita, Sabine Schramm, Sebastian Dolff, Anja Gäckler, Johannes Korth, Falko M. Heinemann, Benjamin Wilde, Mirko Trilling, Peter A. Horn, and et al. 2019. "HLA-E Polymorphism Determines Susceptibility to BK Virus Nephropathy after Living-Donor Kidney Transplant" Cells 8, no. 8: 847. https://doi.org/10.3390/cells8080847