Clonality of B-cells in portal lymphoid infiltrates of HCV-infected livers

Magalini, Alba; Facchetti, Fabio; Salvi, Lucia; Fontana, Lucia; Puoti, Massimo; Scarpa, Aldo

doi:10.1002/(sici)1096-9896(199805)185:1<86::aid-path59>3.0.co;2-r

Cited by 47 publications

(18 citation statements)

References 29 publications

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“…Molecular analyses of B cell clonalities in liver tissue of patients with chronic HCV infection have corroborated previous indications that B lymphocytes recruited at the disease sites are activated and clonally expanded (21,29). The present study shows that monoclonal or oligoclonal B cell expansions were established in 62% (26/42) of unselected patients with HCV-related chronic active liver disease.…”

Section: Discussionsupporting

confidence: 89%

Molecular Characterization of B Cell Clonal Expansions in the Liver of Chronically Hepatitis C Virus-Infected Patients

Racanelli

Sansonno

Piccoli

et al. 2001

The Journal of Immunology

108

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PCR DNA amplification of IgH genes was performed on liver biopsy samples of 42 unselected hepatitis C virus (HCV)-positive patients. Genotypic analysis and signal amplification by branched DNA were used to characterize and quantitate HCV RNA genomic sequences. Intraportal lymphoid follicle-like structures were isolated from surrounding hepatocytes by microdissection technique. IgH VDJ PCR products were cloned and sequenced. IgH VDJ gene rearrangements were detected in the liver of 26 (62%) patients. Unequivocal monoclonal or oligoclonal patterns of B cell expansions were found in 14 (33.3%) and 12 (28.6%) patients, respectively. Patients with intrahepatic B cell monoclonal expansions showed liver HCV RNA levels higher than those with oligoclonal or polyclonal features (1106.4 ± 593.5 vs 677.3 ± 424.3 vs 406.2 ± 354.3 pg HCV RNA/g tissue; p = 0.048 and p = 0.001, respectively). Although a single dominant band was obtained with total DNA, characterization of DNA recovered from intraportal inflammatory aggregates resulted in the detection of multiple IgH VDJ gene rearrangements, pointing to an oligoclonal pattern of lymphoproliferation. Cloning and sequence analyses showed that B cell clonalities were differently distributed in adjacent portal tracts of the same liver area. In addition, HCV RNA genomic sequences could be consistently amplified from each of the portal inflammatory aggregates examined. These data support the concept that in chronic HCV infection the intrahepatic B cell repertoire is frequently clonally restricted and that HCV may have a direct role in sustaining in situ B cell proliferation.

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Section: Discussionsupporting

confidence: 89%

Molecular Characterization of B Cell Clonal Expansions in the Liver of Chronically Hepatitis C Virus-Infected Patients

Racanelli

Sansonno

Piccoli

et al. 2001

The Journal of Immunology

108

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“…Oligoclonal IgH gene rearrangement was recognized in ILFs of chronic hepatitis C. This indicates that clonal B-cell proliferation occurs in the liver, especially with GC formation, perhaps after somatic hypermutation, clonal selection, differentiation, and maturation of the B cell. The frequency of clonal B-cell population (3 of 18 cases) found in the present study is similar to that reported by Sansonno et al, 37 but is lower than that (11 of 11 cases) reported by Magalini et al 38 who also analyzed DNA from paraffin-embedded tissues. The latter group used a microdissection method to isolate a single portal tract containing a lymphoid aggregate from liver tissues and analyzed IgH gene rearrangement by PCR, which could amplify the sensitivity of the assay and could probably be responsible for the different results.…”

Section: Discussionsupporting

confidence: 89%

Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C

et al. 1999

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Hepatitis C virus (HCV) is recognized as a major causative agent of parenterally transmittable non-A, non-B hepatitis. 1 HCV infection often persists for a long time and leads to chronic liver diseases; at least half of the HCV cases develop into chronic hepatitis, and 10% to 20% of cases develop into cirrhosis. 2 The high HCV mutation rate readily generates variants that contribute to establishing the persistent infection. 3

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“…This observation confirms and expands previous descriptions of clonal B-cell population in the blood of HCV-infected persons, as well as clonal B-cell infiltrates in the bone marrow and liver biopsies of patients with HCV infection, associated or not with cryoglobulinemia. [22][23][24][25][26] These infiltrates were shown to remain unmodified during a long follow-up in most cases but can be followed up as overt lymphoma in about 10% of them. The term 'monotypic lymphoproliferative disorder of undetermined significance' 1 has been proposed for these cases.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus-related lymphoproliferative disorders encompass a broader clinical and morphological spectrum than previously recognized: a clinicopathological study

et al. 2014

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We describe a retrospective series of B-cell lymphoproliferative disorders associated with hepatitis C virus infection. In addition to splenic marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma, all of which showed some specific features, we found two poorly described groups of cases. The first featured disseminated marginal zone lymphoma without splenic marginal zone lymphoma features, defying the current marginal zone lymphoma classification; the other consisted of monoclonal B lymphocytes in the peripheral blood, bone marrow or other tissues, with no clinical or histological evidence of lymphoma, and exhibiting a pattern that requires proper identification in order to avoid the misdiagnosis of the lymphoma. Diagnosis of hepatitis C virus infection-associated lymphoproliferative disorders requires the integration of clinical, pathological and molecular findings to establish an adequate diagnosis and decide the appropriate therapy to be applied.

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Clonality of B-cells in portal lymphoid infiltrates of HCV-infected livers

Cited by 47 publications

References 29 publications

Molecular Characterization of B Cell Clonal Expansions in the Liver of Chronically Hepatitis C Virus-Infected Patients

Molecular Characterization of B Cell Clonal Expansions in the Liver of Chronically Hepatitis C Virus-Infected Patients

Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C

Hepatitis C virus-related lymphoproliferative disorders encompass a broader clinical and morphological spectrum than previously recognized: a clinicopathological study

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