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CD81 expression for discrimination between sustained virologic response and relapse in patients with chronic
Martin-Walter Welker1, Wolf Peter Hofmann, Christian Markus Lange
1Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik 1, Frankfurt am Main, Germany.
Insights
Hepatitis C virus (HCV) CD81 expression on B cells can predict treatment outcomes. Higher baseline CD81 on B cells indicates sustained virologic response (SVR) to antiviral therapy, aiding early discrimination between SVR and relapse.
Area of Science:
- Hepatology and Virology
- Immunology
- Biomarker Discovery
Background:
- Hepatitis C virus (HCV) infects hepatocytes and can persist, leading to chronic liver disease.
- CD81, an HCV receptor, is found on peripheral blood mononuclear cells (PBMC) and its expression changes during antiviral therapy.
- Understanding CD81 expression dynamics may help predict treatment success in chronic HCV patients.
Purpose of the Study:
- To prospectively evaluate CD81 expression on PBMC for early prediction of sustained virologic response (SVR) versus relapse (REL).
- To assess CD81 expression changes on lymphocyte subsets during pegylated interferon alfa-2b and ribavirin treatment.
- To determine if baseline CD81 levels can differentiate between SVR and REL in chronic HCV patients.
Main Methods:
- Sixty-one chronic HCV patients (genotype 1, 2, or 3) received pegylated interferon alfa-2b and ribavirin.
- CD81 expression was measured on CD4+, CD8+, CD19+ (B cells), and CD56+ cells using fluorescence-activated cell sorting (FACS).
- Measurements were taken at baseline, therapy week 4, and therapy week 12.
Main Results:
- Baseline CD81 expression on CD4+, CD8+, and CD56+ cells did not differ between SVR and REL groups.
- Higher baseline CD81 expression on CD19+ cells was observed in patients achieving SVR compared to those relapsing (p < 0.006).
- A significant decline in CD81 expression occurred on most lymphocyte subsets in SVR patients, but only on CD8+ and CD56+ cells in REL patients.
Conclusions:
- CD81 expression on B cells (CD19+) at baseline can discriminate between patients who will achieve SVR and those who will relapse.
- Antiviral therapy leads to significant down-regulation of CD81 on various lymphocyte subpopulations.
- Baseline CD81 expression on B cells shows potential as an early predictive biomarker for HCV treatment response.
Background And Aim:
The hepatitis C virus (HCV) receptor CD81 is overexpressed on peripheral blood mononuclear cells (PBMC) in patients chronically infected with HCV compared with healthy controls, and expression declines during antiviral therapy. The aim of this study was to prospectively investigate CD81 expression on PBMC for early discrimination between sustained virologic response (SVR) and relapse (REL) to pegylated interferon alfa-2b and ribavirin treatment.
Methods:
Sixty-one patients with chronic HCV infection (genotype, GT, 1 and low baseline viremia <600,000 IU/ml, n = 30; GT 2 or 3, n = 31) were investigated. CD81 expression on CD4(+), CD8(+), CD19(+), and CD56(+) cells was measured at baseline, therapy week (TW) 4 and 12 during antiviral therapy by fluorescence-activated cell sorting (FACS) analysis.
Results:
Baseline levels of CD81 on CD4(+), CD8(+), and CD56(+) cells were similar between patients who achieved a SVR (n = 42) and those who relapsed (n = 19). On CD19(+) cells, baseline CD81 expression was higher in patients with SVR than in patients with virologic relapse (REL) (p < 0.006). A cutoff value of 720 relative fluorescence units (RFU) discriminated correctly between SVR and REL with a sensitivity and specificity of 73.7% and 66.7%, respectively. SVR patients showed a significant decline of CD81 expression on CD4(+), CD8(+), CD19(+), and CD56(+) cells (p < 0.01 for all) while in REL patients a significant decline of CD81 expression was observed on CD8(+) and CD56(+) cells, only (p = 0.050 and p = 0.038, respectively).
Conclusions:
The current study confirms significant down-regulation of CD81 expression on different lymphocyte subpopulations during pegylated interferon alfa-based antiviral therapy in patients with chronic hepatitis C. Baseline CD81 expression on CD19(+) cells was found to discriminate between SVR and REL.
