Advanced liver disease due to hepatitis C infection is associated with reduced CD19+CD27+ memory B-cells (100.29)

Abstract

Abstract Advanced neoplasia is associated with defects in B-cell memory. Hepatocellular carcinoma (HCC) frequently arises in the setting of hepatitis C-induced cirrhosis. We hypothesized that memory B-cells from patients with HCC would be reduced in frequency relative to non-cancer bearing cirrhotics and non-cirrhotic HCV. We studied PBMC samples from HCC+ HCV+ cirrhotic patients (n=12), HCC- HCV+ cirrhotic patients (n=12), HCC- HCV+ non-cirrhotic patients (n=10), and HCV- normal donors (n=10) for surface expression of CD19, CD21, CD27, and FcRL4. The frequency of CD27+ memory cells among CD19+ B-cells was significantly lower in patients with cirrhosis (± HCC) compared to HCV+ non-cirrhotic patients (mean ± SE, 16.0 ± 2.7 vs. 29.7 ± 3.8%, p = 0.007) and normal donors (p=0.034). The frequency of atypical memory B-cells (CD27-CD21-/CD19+) was significantly greater among HCC+ patients (31.1 ± 3.7%) compared to HCC- cirrhotics (19.0 ± 3.5%, p=0.023), non-cirrhotic HCV+ patients (16.4 ± 3.9%, p=0.009) and normal donors (17.3 ± 3.9%, p=0.014). Among HCC patients, there was a positive correlation between CD27-CD21- B-cell frequency and AFP levels (R2 = 0.55, p=0.04). Conclusions: HCV-induced cirrhosis is associated with loss of CD19+CD27+CD21+ memory B-cells, while HCC is associated with an increase in CD19+CD27-CD21- atypical memory B cells. These findings identify a phenotype that may be associated with immunodeficiency in cirrhosis as well as with tumor-induced immune suppression in HCC.