Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. Tissue Material
2.2.1. Histological Preparation
2.2.2. Histopathological Evaluation
2.2.3. Digitization and Digital Analysis
2.3. Cytofluorometric Analysis
2.4. Statistical Analysis
- For unrelated quantitative variables, after checking the test assumptions (Shapiro–Wilk test, Levene test) using parametric tests (t-tests), non-parametric tests (Mann–Whitney U test) were used if the assumptions were not met.
- For qualitative variables, the following tests were used: Pearson’s Chi2 and Maximum Likelihood.
- The direction and strength of the association between the two quantitative variables was assessed using the regression equation and Pearson’s linear correlation coefficient or Spearman’s R nonparametric correlation.
- In all analyses, p < 0.05 was considered significant. Each subgroup of patients was analyzed separately, the groups were not intermixed.
3. Results
3.1. Analysis of Natural Killer Cell Phenotypes in Whole Blood within Groups
3.1.1. Percentage of CD16+ Natural Killer Cells (Antibody Mix 1)
3.1.2. Percentage of NKCD16+ Natural Killer Cells (Antibody Mix 2)
3.1.3. Percentage of CD62L+ Natural Killer Cells
3.1.4. Percentage of CD62L+ CD94++ Cells
3.1.5. Percentage of CD27+ Cells
3.1.6. Percentage of CD127+ and CD27+ Natural Killer Cells
3.1.7. Percentage of CXCR3+ CD27+ Cells
3.2. Analysis of Intrahepatic NK Cells in Groups
3.3. Analysis of the Correlation between the Percentage of NK Cells in Whole Peripheral Blood and the Liver
3.3.1. Peripheral Blood CD62L+ NK Percentage vs. NK Cell Population Density in the Liver
3.3.2. Percentage of CD94+ NK Cells in Peripheral Blood vs. Percentage of CD56 NK Cells in the Liver
3.3.3. Percentage of CXCR3+ and CD94+ Natural Killer Cells in Peripheral Whole Blood vs. Population Density of CD56 Lymphocytes in the Liver
3.3.4. Correlation of CXCR3+ CD94+ NK Percentage in Whole Peripheral Blood a Percentage of Intrahepatic CD56+ Lymphocytes in the Group of Patients with Advanced Liver Fibrosis/Cirrhosis (≥F3)
3.3.5. Correlation of the Percentage of CXCR3+CD94+ in Peripheral Blood and the Population Index of Intrahepatic CD56+ Lymphocytes in the Group of Patients with Advanced Liver Fibrosis (≥F3)
3.3.6. Percentage of CD94+ Natural Killer Cells in Peripheral Whole Blood a Population Index of Intrahepatic Lymphocytes in the Group of Patients with None/Mild/Moderate Fibrosis
3.3.7. Correlation of the Percentage of Cells with the CD94++ NK Phenotype in Peripheral Blood and the Population Index of Intrahepatic Lymphocytes in the Group of Patients with None/Mild/Moderate Fibrosis
4. Discussion
5. Conclusions
- Patients with CHC with advanced liver fibrosis ≥ F3 have a higher percentage of the total population of CD56+ CD16+ NK cells in peripheral blood compared to patients with mild or moderate fibrosis.
- There is a higher percentage of NK cells with CD62L+, CD94+, CD27+, CD127+ and CXCR3+ phenotypes in the peripheral blood of patients with mild or moderate fibrosis in relation to patients with advanced liver fibrosis or cirrhosis. This indicates a lower availability of functionally active NK cells in the peripheral blood of patients with advanced fibrosis.
- In patients with CHC, there is a positive correlation between the percentage of NK cells with CD62L+ and CD62L+ CD94+ phenotypes in peripheral blood and the population index of intrahepatic NK cells, regardless of the extent of fibrosis.
- The percentage of NK cells with the CXCR3+ CD94+ phenotype in the peripheral blood was correlated with the population index and the percentage of NK cells in the liver, with the correlation increasing depending on the degree of fibrosis.
- In patients with CHC with advanced liver fibrosis, there is intrahepatic accumulation of functionally impaired natural killer cells, thus limiting their influence on further progression of fibrosis.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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FITC | PE | PerCP-Cy5.5 | PE-Cy7 | APC | APC-Ax750 | Pacific Blue | V500 | |
---|---|---|---|---|---|---|---|---|
1 | CD7 | CD62L | CD16 | CXCR3 | CD94 | CD3 | CD56 | CD45 |
2 | CD7 | CD127 | CD16 | CXCR3 | CD27 | CD3 | CD56 | CD45 |
NK CD16+ | n | Mean Value ± Standard Deviation | |
---|---|---|---|
None/mild/moderate fibrosis (F0/F1/F2) | antibody mix 1 | 41 | 90.70 ± 6.69 * |
antibody mix 2 | 89.36 ± 6.84 * | ||
Advanced hepatic fibrosis/cirrhosis (F3/F4) | antibody mix 1 | 15 | 95.49 ± 1.87 * |
antibody mix 2 | 93.95 ± 3.56 * | ||
Total in the group | antibody mix 1 | 56 | 91.98 ± 6.17 |
antibody mix 2 | 90.64 ± 6.42 |
Group of Patients | n | Analyzed Parameter | Mean Value ± Standard Deviation |
---|---|---|---|
None/mild/moderate fibrosis (F0/F1/F2) | 41 | % of intrahepatic CD56 cells | 8.12 ± 0.10 |
population index of intrahepatic CD56 | 7.02 ± 6.12 | ||
Advanced hepatic fibrosis/cirrhosis (F3/F4) | 15 | % of intrahepatic CD56 cells | 5.61 ± 0.05 |
population index of intrahepatic CD56 | 5.82 ± 5.05 | ||
Total in the group | 56 | % of intrahepatic CD56 cells | 7.45 ± 0.09 |
population index of intrahepatic CD56 | 6.69 ± 5.73 |
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Kleczka, A.; Mazur, B.; Tomaszek, K.; Gabriel, A.; Dzik, R.; Kabała-Dzik, A. Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C. Diagnostics 2023, 13, 2187. https://doi.org/10.3390/diagnostics13132187
Kleczka A, Mazur B, Tomaszek K, Gabriel A, Dzik R, Kabała-Dzik A. Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C. Diagnostics. 2023; 13(13):2187. https://doi.org/10.3390/diagnostics13132187
Chicago/Turabian StyleKleczka, Anna, Bogdan Mazur, Krzysztof Tomaszek, Andrzej Gabriel, Radosław Dzik, and Agata Kabała-Dzik. 2023. "Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C" Diagnostics 13, no. 13: 2187. https://doi.org/10.3390/diagnostics13132187