Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia—Any Link with Known Prognostic Factors?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Preparation of Material
2.3. Immunophenotyping
2.4. Leukemia Cell Genotyping
2.5. DNA Isolation and Calculation of EBV Load
2.6. Measurement of EBV-Specific Antibodies in Serum
2.7. Measurement of Lactic Dehydrogenase and Beta-2 Microglobulin Concentrations in Serum
2.8. Statistical Analysis
3. Results
4. Discussion
5. Limitations of the Study
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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EBV(+) Patients with CLL | EBV(−) Patients with CLL | Controls | p | |
---|---|---|---|---|
N | 59 | 51 | 20 | |
AGE, YEARS, MEAN (SD) | 63.81 (9.37) | 63.63 (10.76) | 64.50 (7.15) | 0.943 |
WHITE BLOOD CELL COUNT G/L, MEDIAN [IQR] | 28.30 [20.47, 48.92] | 30.40 [19.85, 46.72] | 7.02 [6.12, 7.85] | <0.001 a |
LYMPHOCYTE COUNT G/L, MEDIAN [IQR] | 22.44 [15.40, 43.01] | 22.58 [14.93, 40.55] | 2.62 [2.19, 3.05] | <0.001 a |
HEMOGLOBIN, G/DL, MEAN (SD) | 12.09 (1.42) | 14.12 (1.27) | 14.29 (1.19) | <0.001 b |
PLATELET COUNT, G/L, MEAN (SD) | 150.02 (58.07) | 180.51 (46.98) | 279.00 (57.05) | <0.001 c |
BETA-2 MICROGLOBULIN, MG/DL, MEDIAN [IQR] | 3.47 [2.78, 4.23] | 2.37 [1.98, 2.87] | 1.68 [1.29, 1.91] | <0.001 c |
LACTATE DEHYDROGENASE, U/L MEDIAN [IQR] | 327.00 [290.50, 378.00] | 254.00 [214.50, 334.00] | 155.50 [137.00, 178.25] | <0.001 c |
RAI STAGE (%) | 0.06 | |||
0 | 24 (40.7) | 24 (47.1) | - | |
I | 11 (18.6) | 15 (29.4) | - | |
II | 16 (27.1) | 12 (23.5) | - | |
III | 2 (3.4) | 0 (0.0) | - | |
IV | 6 (10.2) | 0 (0.0) | - | |
BINET CLASSIFICATION (%) | 0.018 | |||
A | 24 (40.7) | 24 (47.1) | - | |
B | 27 (45.8) | 27 (52.9) | - | |
C | 8 (13.6) | 0 (0.0) | - | |
CD19+ ZAP70+ CELLS > 20%, N (%) | 27 (45.8) | 11 (21.6) | - | 0.009 |
CD19+ CD38+ CELLS > 30%, N (%) | 34 (57.6) | 6 (11.8) | - | <0.001 |
CD19+ ZAP70+ CELLS, % MEDIAN [IQR] | 17.96 [11.09, 29.04] | 5.80 [3.22, 18.19] | - | <0.001 |
CD19+ CD38+ CELLS, % MEDIAN [IQR] | 33.53 [12.02, 59.89] | 1.64 [0.78, 6.27] | - | <0.001 |
Variable | Group | Median | Minimum | Maximum | p |
---|---|---|---|---|---|
LYMPHOCYTES CD19+/CD86+ [%] | EBV(+) | 35.37 | 4.43 | 75.6 | <0.0001 0.0002 |
EBV(−) | 16.73 | 1.5 | 46.99 | ||
Control | 11.32 | 2.98 | 18.19 | ||
ABSOLUTE NUMBER OF LYMPHOCYTES CD19+/CD86+ [X103 CELLS/UL] | EBV(+) | 6.4495 | 0.4433 | 32.656 | 0.0354 <0.0001 0.0256 |
EBV(−) | 2.5725 | 0.2094 | 22.0708 | ||
Control | 0.0292 | 0.0108 | 0.0403 | ||
CD86 ANTIGEN EXPRESSION ON LYMPHOCYTES CD19+ [MFI] | EBV(+) | 21.83 | 14.18 | 131.24 | 0.0256 0.0067 |
EBV(−) | 18.655 | 14.24 | 29.44 | ||
Control | 15.495 | 13.24 | 18.97 |
Variable | Group | Median | Minimum | Maximum | p |
---|---|---|---|---|---|
LYMPHOCYTES CD3+/CTLA-4+ (AMONG CD3+) [%] | EBV(+) | 5.41 | 2.13 | 14.36 | 0.0395 |
EBV(−) | 4.715 | 1.95 | 8.06 | ||
Control | 2.975 | 1.34 | 5.8 | ||
ABSOLUTE NUMBER OF LYMPHOCYTES CD3+/CTLA-4+ (AMONG CD3+) [X103 CELLS/UL] | EBV(+) | 0.1433 | 0.0356 | 0.423 | 0.0078 0.0314 |
EBV(−) | 0.1515 | 0.0407 | 0.289 | ||
Control | 0.0542 | 0.0129 | 0.0787 | ||
LYMPHOCYTES CD4+/CTLA-4+ (AMONG CD4+) [%] | EBV(+) | 14.755 | 9.56 | 31.14 | 0.0012 0.0001 0.0091 |
EBV(−) | 8.435 | 5.96 | 14.25 | ||
Control | 2.85 | 2.17 | 3.19 | ||
ABSOLUTE NUMBER OF LYMPHOCYTES CD4+/CTLA-4+ (AMONG CD4+) [X103 CELLS/UL] | EBV(+) | 0.1705 | 0.0913 | 0.908 | 0.0001 0.0150 |
EBV(−) | 0.1367 | 0.0761 | 0.2681 | ||
Control | 0.0303 | 0.0147 | 0.0406 | ||
LYMPHOCYTES CD8+/CTLA-4+ (AMONG CD8+) [%] | EBV(+) | 16.855 | 11.38 | 26.69 | 0.0001 0.0001 0.0011 |
EBV(−) | 8.785 | 5.91 | 13.75 | ||
Control | 2.835 | 1.58 | 3.89 | ||
ABSOLUTE NUMBER OF LYMPHOCYTES CD8+/CTLA-4+ (AMONG CD8+) [X103 CELLS/UL] | EBV(+) | 0.1903 | 0.0322 | 1.487 | 0.0002 0.0420 |
EBV(−) | 0.1166 | 0.0295 | 0.2913 | ||
Control | 0.0155 | 0.0101 | 0.0378 | ||
EXPRESSION OF CTLA-4 ON CD8+ [MFI] | EBV(+) | 28.185 | 26.22 | 34.52 | 0.0434 |
EBV(−) | 28.38 | 25.43 | 29.52 | ||
Control | 22.895 | 17.57 | 37.65 | ||
ABSOLUTE NUMBER OF LYMPHOCYTES CD19+/ CTLA-4+(AMONG CD19+) [X103 CELLS/UL] | EBV(+) | 1.1267 | 0.1395 | 8.676 | 0.0005 0.0019 |
EBV(−) | 0.9997 | 0.148 | 6.3925 | ||
Control | 0.0056 | 0.0034 | 0.0203 |
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Grywalska, E.; Mielnik, M.; Podgajna, M.; Hymos, A.; Ludian, J.; Rolińska, A.; Gosik, K.; Kwaśniewski, W.; Sosnowska-Pasiarska, B.; Smok-Kalwat, J.; et al. Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia—Any Link with Known Prognostic Factors? Cancers 2022, 14, 672. https://doi.org/10.3390/cancers14030672
Grywalska E, Mielnik M, Podgajna M, Hymos A, Ludian J, Rolińska A, Gosik K, Kwaśniewski W, Sosnowska-Pasiarska B, Smok-Kalwat J, et al. Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia—Any Link with Known Prognostic Factors? Cancers. 2022; 14(3):672. https://doi.org/10.3390/cancers14030672
Chicago/Turabian StyleGrywalska, Ewelina, Michał Mielnik, Martyna Podgajna, Anna Hymos, Jarosław Ludian, Agnieszka Rolińska, Krzysztof Gosik, Wojciech Kwaśniewski, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, and et al. 2022. "Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia—Any Link with Known Prognostic Factors?" Cancers 14, no. 3: 672. https://doi.org/10.3390/cancers14030672