Hepatitis C virus (HCV), being lymphotrophic as well as hepatotrophic, has been reported to induce B-cell proliferative disorders such as mixed cryoglobulinemia and B-cell lymphoma. To investigate the association between HCV and B-cell proliferation, we evaluated the incidence and characteristics of monoclonal B cells in the circulating blood of HCV-infected cases relative to controls with non-HCV hepatic diseases. We first evaluated the surface immunoglobulin κ:λ light-chain ratios of the circulating B (CD19+) cells in 240 HCV-infected cases and 150 controls. Light chain restriction (κ:λ ratio >3:1 or < 1:2) was detected in 7 cases with HCV (2.9%) (Table 1), but was never detected in the controls (p<0.05). As these monoclonal B cells were not identified morphologically, they were analyzed for CD5/CD20 expression. None of them showed the so-called chronic lymphocytic leukemia (CLL)-phenotype cells. The clonal and normal B cells did not differ significantly in their intensity of CD5 expression (Figure 1). The B-cell clonality was confirmed in all 7 cases by polymerase chain reaction (PCR) analysis of the immunoglobulin heavy-chain (IgH) gene rearrangements and the t(14;18) fusion gene was detected in one case. The loss of clonality was observed in 2 cases treated with interferon and in one case treated with splenectomy. The longitudinal study is required to determine whether these circulating monoclonal B cells progress to lymphoproliferative disorders or not.

Table 1. The clinical data of the 7 HCV-infected cases with monoclonal H cells

Case NoAgeSexWBC count./ulLymphocyte count./ulCD19+ cells in lymphocytes. %Light chainκ/λ.CD5+B cell. %CryoglobulinIFN therapy
1 78 M 2,800 710 26.46 κ 33.59 17.45 (+) (−) 
2 65 M 3,400 720 5.41 λ 0.23 15.93 (−) (+) 
3 84 M 5,700 3,520 46.68 κ 11.31 6.8 (+) (−) 
4 74 F 3,300 1,750 15.01 λ 0.037 46.31 (−) (−) 
5 65 F 2,500 580 34.46 κ 8.07 40.17 (+) (−) 
6 72 F 2,000 940 25.4 λ 0.198 38.77 (−) + 
7 66 M 4,200 1,380 9.73 λ 0.41 3.53 (+) (−) 
Case NoAgeSexWBC count./ulLymphocyte count./ulCD19+ cells in lymphocytes. %Light chainκ/λ.CD5+B cell. %CryoglobulinIFN therapy
1 78 M 2,800 710 26.46 κ 33.59 17.45 (+) (−) 
2 65 M 3,400 720 5.41 λ 0.23 15.93 (−) (+) 
3 84 M 5,700 3,520 46.68 κ 11.31 6.8 (+) (−) 
4 74 F 3,300 1,750 15.01 λ 0.037 46.31 (−) (−) 
5 65 F 2,500 580 34.46 κ 8.07 40.17 (+) (−) 
6 72 F 2,000 940 25.4 λ 0.198 38.77 (−) + 
7 66 M 4,200 1,380 9.73 λ 0.41 3.53 (+) (−) 
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Figure 1.
Figure 1. The three groups did not differ significantly in the frequency of CD5+ B cells (mean±SEM: group1, 24.14±6.55; group2, 30.27±1.69; group3, 28.53±1.93).
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The three groups did not differ significantly in the frequency of CD5+ B cells (mean±SEM: group1, 24.14±6.55; group2, 30.27±1.69; group3, 28.53±1.93).

Figure 1.
Figure 1. The three groups did not differ significantly in the frequency of CD5+ B cells (mean±SEM: group1, 24.14±6.55; group2, 30.27±1.69; group3, 28.53±1.93).
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The three groups did not differ significantly in the frequency of CD5+ B cells (mean±SEM: group1, 24.14±6.55; group2, 30.27±1.69; group3, 28.53±1.93).

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Topics:
antigens, cd98 light chains, b-lymphocytes, cd20 antigens, chronic b-cell leukemias, chronic lymphocytic leukemia, clonality (genetic analysis), cryoglobulins, hepatitis c, human leukocyte interferon, idiopathic guttate hypomelanosis

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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