Hepatitis C Virus and Immunoglobulin Gene Rearrangements: An Early Step in Lymphomagenesis?

Santini, G; Crovatto, M; Giannini, F.; Bortolin, Monica; Mazzaro, Cesare; Invernizzi, F

doi:10.1159/000040885

Cited by 8 publications

(6 citation statements)

References 24 publications

(24 reference statements)

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“…In addition, clonal B cell expansion could have been missed due to numerous somatic mutations in the IgH genes. We also observed a clonal B cell population in 3 of 12 HCV‐infected patients with type III polyclonal cryoglobulins and in 14 of 44 patients without MC, a finding in concordance with the results of previous studies (16, 17).…”

Section: Discussionsupporting

confidence: 92%

“…In Italian studies, the prevalence of HCV infection among patients with NHL varied from 9% to 42%. Among Italian patients with chronic HCV infection, cryoglobulins were observed in 24–53% of cases, B cell expansion in the blood was reported in 55–86% of cases, and B cell expansion in liver samples was observed in 62–100% of cases (15–22). In France, the prevalence of HCV infection among patients with NHL varied from 2% to 2.5% and was similar to the prevalence in control groups.…”

Section: Discussionmentioning

confidence: 99%

“…Immunoglobulins are directed toward viral proteins (10, 14). B cell clonal expansion has been reported in small cohorts of HCV‐infected patients, more frequently in those who are mixed cryoglobulin positive (15–18). Clonal B cell proliferation has also been observed in liver biopsy specimens obtained from Italian patients with HCV infection (19–23).…”

mentioning

confidence: 99%

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Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection

Vallat¹,

Benhamou²,

Gutierrez³

et al. 2004

Arthritis & Rheumatism

107

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Objective. The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liverinfiltrating monoclonal B cells in patients with HCV infection.Methods. One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis.Results. A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV-infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P ‫؍‬ 0.004) and had longer duration of HCV infection (P ‫؍‬ 0.009), higher serum cryoglobulin levels (P ‫؍‬ 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P ‫؍‬ 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed.Conclusion. Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection

Vallat¹,

Benhamou²,

Gutierrez³

et al. 2004

Arthritis & Rheumatism

107

View full text Add to dashboard Cite

show abstract

“…Both HCV and HBV are able to infect blood mononuclear cells, including B and T lymphocytes and monocytes (Bouffard et al , 1992; Zignego et al , 1992). HCV has been shown to induce clonal B‐cell immunoglobulin gene rearrangements in infected patients in the absence of overt lymphoproliferative disease (Santini et al , 1998). Mixed cryoglobulinaemia (MC), a clonal B‐cell disorder associated with an increased risk of lymphomagenesis, is preceded by HCV infection in up to 95% of the cases (Ferri et al , 1993; Pozzatto et al , 1994).…”

Section: Discussionmentioning

confidence: 99%

“…However, similar studies in Northern Europe have not confirmed these findings (McColl et al , 1996). Both HCV and HBV are lymphotropic and hepatotropic viruses and may lead to clonal expansion of B lymphocytes (Franzini et al , 1995; Santini et al , 1998). Romania is an endemic region for HBV and the rate of HCV infection in the general population is similar to that in Southern Europe (around 5%), much higher than in Northern Europe (Paquet et al , 1993; Molnar et al , 1994).…”

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confidence: 99%

Hepatitis B and C virus infection in Romanian non‐Hodgkin's lymphoma patients

Cucuianu¹,

Patiu²,

Duma³

et al. 1999

Br J Haematol

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Summary. We determined the hepatitis C virus (HCV) antibodies (anti-HCV) and the hepatitis B virus (HBV) surface antigen (HBsAg) in a cohort of 68 consecutive non-Hodgkin's lymphoma (NHL) patients diagnosed and treated in our institution between December 1997 and March 1999. 27 cases were diagnosed as low-grade, 33 as intermediate-grade, and eight as high-grade NHL. In 35 cases (51´4%) we found evidence of either HCV or HBV infection. Anti-HCV antibodies were found in 20 patients (29´5%) and HBsAg was found in 21 patients (30´8%). In six patients both anti-HCV and HBsAg were present. Anti-HCV were present in 12/27 low-grade NHL cases (44´4%) and in 8/41 intermediate/high-grade (aggressive) NHL cases (19´5%, P < 0´03). HBsAg was found in 10/27 low-grade NHL cases (37%) and in 11/41 aggressive NHL cases (26´8%). Evidence of liver disease, as re¯ected by elevated aminotransferases or typical alterations at liver biopsy, was present in eight patients. Cryoglobulins were present in six patients, all anti-HCV positive and with low-grade NHL. The prevalence of both HCV antibodies and HBsAg was signi®cantly higher (P < 0´0001) in our NHL cases than in a sample of the general Romanian population, where the prevalence of anti-HCV was 4´9% and that of HBsAg was 6´3%. It is dif®cult to say whether either HCV or HBV had actually been involved in lymphomagenesis or if a-interferon treatment would be effective in this subset of patients.

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The role of the hepatitis C virus glycoproteins in infection

Flint

McKeating

2000

Rev. Med. Virol.

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Hepatitis C Virus and Immunoglobulin Gene Rearrangements: An Early Step in Lymphomagenesis?

Cited by 8 publications

References 24 publications

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection

Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection

Hepatitis B and C virus infection in Romanian non‐Hodgkin's lymphoma patients

The role of the hepatitis C virus glycoproteins in infection

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