The B-cell receptor of a hepatitis C virus (HCV)–associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3745-3749 ◽  
Author(s):  
Elizabeth R. Quinn ◽  
Chunghuang Hubert Chan ◽  
Kenneth G. Hadlock ◽  
Steven K. H. Foung ◽  
Mike Flint ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Receptor ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Test Cases ◽  
E2 Protein ◽  
Non Hodgkin Lymphoma ◽  
Bona Fide

Abstract Hepatitis C virus (HCV) infection is associated with extrahepatic B-cell lymphoproliferative disorders. To determine whether a viral antigen drives this B-cell expansion, the B-cell receptors were cloned from HCV-associated lymphomas and were expressed as soluble immunoglobulins. The rescued immunoglobulins were then tested for their ability to bind the HCV-E2 envelope glycoprotein, an antigen that was previously implicated in the pathogenesis of HCV-associated B-cell diseases. One of 2 lymphoma immunoglobulin test cases bound the E2 protein in a manner identical to a bona fide human anti-E2 antibody. Moreover, it bound E2 from multiple viral genotypes, suggesting reactivity with a conserved E2 epitope. These findings support the hypothesis that some HCV-associated lymphomas originate from B cells that were initially activated by the HCV-E2 protein and might explain the association between HCV infection and some B-cell lymphoproliferative disorders.

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4296-4301 ◽  
Author(s):  
F Silvestri ◽  
C Pipan ◽  
G Barillari ◽  
F Zaja ◽  
R Fanin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Close Association ◽  
Mixed Cryoglobulinemia ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hodgkin's Lymphomas ◽  
Hcv Genotyping

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B- cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti- HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV- positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

scholarly journals Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Kyoko Tsukiyama-Kohara ◽  
Satoshi Sekiguchi ◽  
Yuri Kasama ◽  
Nagla Elwy Salem ◽  
Keigo Machida ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Mouse Model ◽  
B Cell ◽  
Lymphoproliferative Disorder ◽  
Interleukin 2 ◽  
Elevated Serum ◽  
Hcv Infection ◽  
Α Subunit ◽  
Non Hodgkin Lymphoma

B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes.

scholarly journals High prevalence of Hepatitis C Virus associated B-cell lymphoma in Mansoura Region (Egypt), ANRS 12263 study

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Layla M. Saleh ◽  
Danielle Canioni ◽  
Sameh Shamaa ◽  
Maha El-Zaafarany ◽  
Ziad Emarah ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Treatment ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Delta Region ◽  
Genotype 4 ◽  
Non Hodgkin Lymphoma

Abstract : Background: The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. Objectives: We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in Delta region (Mansoura-Egypt). Methods: Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing and for HCV RNA. Results: The prevalence of HCV infection among these patients was 61% (67/110 patients) which is the highest reported value in literature. Among them, 80% (32/40 tested patients) presented with viremia. Contrasting with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72 %) followed by SLL/CLL (13 %), follicular lymphomas (7.5%) and 7.5% of marginal zone lymphomas. In conclusion:  B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for those patients in Delta region. 

scholarly journals Hepatitis C Virus-Induced Exosomal MicroRNAs and Toll-Like Receptor 7 Polymorphism Regulate B-Cell Activating Factor

mBio ◽  
2021 ◽  
Author(s):  
Tsai-Ling Liao ◽  
Yi-Ming Chen ◽  
Shie-Liang Hsieh ◽  
Kuo-Tung Tang ◽  
Der-Yuan Chen ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Toll Like Receptor ◽  
B Cell Activating Factor

HCV remains an important cause of liver disease worldwide. Accumulating evidence has demonstrated that HCV infection is associated with B cell lymphoproliferative disorders such as MC.

scholarly journals Hepatitis C Virus Infection and Mixed Cryoglobulinemia

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gianfranco Lauletta ◽  
Sabino Russi ◽  
Vincenza Conteduca ◽  
Loredana Sansonno
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Clonal Selection ◽  
Biological Activities ◽  
Clinical Manifestations ◽  
Mixed Cryoglobulinemia ◽  
Hcv Infection ◽  
Host Immune System ◽  
Inflammatory Infiltrates

Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures.

scholarly journals Occult hepatitis C virus infection in patients with malignant lymphoproliferative disorders

2020 ◽  
Vol 34 ◽  
pp. 205873842096120
Author(s):  
Abeya A Lotfi ◽  
Asmaa E Mohamed ◽  
Nahela A Shalaby ◽  
Deena S Eissa ◽  
Ehab El-Dabaa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Treatment Protocol ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hepatitis C Virus Infection ◽  
Occult Hepatitis ◽  
Occult Hepatitis C

Despite the link between HCV and malignant lymphoproliferative disorders has been established, the association between occult hepatitis C virus infection and malignant lymphoproliferative disorders remains obscure. The present study intended to identify the possible association between occult HCV infection and malignant lymphoproliferative disorders. Newly diagnosed patients with LPDs were screened for the presence of HCV-RNA in both plasma and PBMCs. PBMCs of the subjects were also, examined by transmission and immuno-electron microscopy. LPD patients showed a high percentage of HCV infection (71.9%): OCI-HCV (37.5%) and HCV (34.38%). Meanwhile, 28.13% of LPD patients did not show any evidence of HCV infection. Ultrastructural examination of PBMCs revealed the presence of intracytoplasmic vacuoles enclosing viral like particles, which were less prominent in occult HCV patients. The possibility of occult HCV should be considered in patients with LPDs which can be helpful in the management of the treatment protocol in order to set up a balance between the control of the tumor progression and minimizing post chemotherapy complications related to HCV infection.

Sign in / Sign up

Export Citation Format

Share Document