Significance of IgG and IgM HCV antibody secretion in vitro in patients with chronic hepatitis C: Correlation with disease activity and response to interferon-α

Löhr, Hanns; Nagel, Christopher; Dienes, Hans‐Peter; Simpson, B.; Michel, Gerd; Goergen, Bernd; Büschenfelde, Karl‐Hermann Meyer zum; Gerken, Guido

doi:10.1002/hep.1840200602

Cited by 12 publications

(3 citation statements)

References 40 publications

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“…Comparison of untreated and treated non-responders patients showed clearly that treatment with IFNa and/or ribavirin suppresses the anti-HCV antibodies secretion in vitro. We could not find any secretion in responders and long-term responders in accordance with Lohr et al [1994] which showed that the HCV antibody-negative patients were mostly responders to IFNa therapy. It has been hypothesized that persistent antigenic stimulation is responsible for the production of HCV-specific antibodies by B lymphocytes in vitro.…”

Section: Discussionsupporting

confidence: 91%

“…Specific antibody secretion in vitro was demonstrated in patients with chronic hepatitis C, although differences in the level of production were observed [Ducos et al, 1994;Lohr et al, 1994;Quinty et al, 1995]. Comparison of untreated and treated non-responders patients showed clearly that treatment with IFNa and/or ribavirin suppresses the anti-HCV antibodies secretion in vitro.…”

Section: Discussionmentioning

confidence: 96%

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Analysis of B‐lymphocyte differentiation in patients infected with hepatitis C virus

Fournillier

Freida

Defrance

et al. 2004

Journal of Medical Virology

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To clarify whether some of the functions of B lymphocytes could be affected during hepatitis C virus (HCV) infection, phenotypic characteristics of B lymphocytes from HCV-infected patients and their capacity to differentiate into immunoglobulins (Ig)-secreting cells were studied. B lymphocytes differentiation was investigated for patients untreated and non-responders (n=9), treated and non-responders (n=6), responders (n=6), long-term responders (n=9) to therapy and seronegative controls (n=14) following in vitro stimulation with S. aureus strain Cowan I mitogen. HCV sequences in purified B lymphocytes were detected by RT-PCR. It was found that HCV-patients harbor a similar mean percentage of B cells and a normal level of naïve B cells (% IgM+/IgD+ cells=79.7 +/- 15.4 for untreated non-responders, 57.1 +/- 22.9 for treated non-responders, 44.3 +/- 29.1 for responders, 75.7 +/- 16 for long-term responders) as compared with controls. It was also found that peripheral blood mononuclear cells (PBMCs) of patients or controls produced similar amounts of IgG, A, and M in vitro. A total of 57% of untreated non-responders versus 17% of treated non-responders were able to produce HCV-specific antibodies. Interestingly, B lymphocytes from PBMCs able to secrete anti-HCV antibodies contained HCV positive strand RNA, although no systematic detection of the negative strand was found. These data suggest that signaling through the B cell receptor (BCR) in B lymphocytes of HCV-infected patients appears normal whatever their response to therapy. The capacity to secrete HCV-specific IgG seemed to be linked to the presence of positive strand RNA rather than virus replication.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Analysis of B‐lymphocyte differentiation in patients infected with hepatitis C virus

Fournillier

Freida

Defrance

et al. 2004

Journal of Medical Virology

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“…We have also developed and evaluated the ELISpot assay for detecting anti‐HCV IgM‐secreting B cells. It has been reported that IgM anti‐HCV in serum might be predictive of viral clearance in acute hepatitis C or response to interferon therapy 36–40. However, these results have been controversial and other studies have shown a significant correlation between IgM anti‐HCV levels in serum and the recurrence of hepatitis C after liver transplantation 41, 42.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of anti–hepatitis C virus antibody–secreting B cells in patients with chronic hepatitis C†

et al. 2006

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H epatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. More than half of patients with acute HCV infection develop chronic hepatitis, leading to cirrhosis and/or hepatocellular carcinoma in at least 20% of these patients. [1][2][3] Chronic HCV infection results in the induction of a strong humoral immune response, and measurement of anti-HCV antibodies in serum is widely used to screen for HCV infection. Although several studies have examined the features of the humoral immune response to HCV, 4-7 the quantitative characteristics of HCV-specific antibody production during infection remain undefined. In patients with acute hepatitis C, an early HCV-specific T-cell response is associated with viral clearance, [8][9][10][11] but the role of humoral immune responses in HCV clearance is unclear and appears to be subsidiary, because strong antibody responses are detected in all immunocompetent chronic HCV carriers. It is also unknown whether anti-HCV antibodies serve to control the level of viremia during chronic infection and whether they ameliorate horizontal or vertical transmission.An enzyme-linked immunosorbent spot (ELISpot) assay for detecting individual B cells secreting specific antibodies has enabled investigators to study B-cell immunity at a cellular level in a variety of clinical applications. 12,13 The advantages of the ELISpot assay are that it can detect even a single cell out of 10 6 peripheral blood mononuclear cells (PBMCs), whose secretion level may not be sufficient for detection of circulating antibody, and distinguishes and quantifies only active immunoglobulin-secreting

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Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy

et al. 1997

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Hepatitis C virus (HCV) appears to circulate in various forms such as native virion, immune complexes, and nucleocapsids during chronic infections. To determine the association of the physicochemical properties of HCV and its response to interferon therapy in patients with chronic hepatitis C, we examined pretreatment serum samples from 43 patients with HCV RNA who had received interferon therapy, using differential flotation centrifugation in a NaCl solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA in the top and bottom fractions was determined by the polymerase chain reaction and expressed as T/B. Patients with a sustained response to IFN therapy were found to have higher T/B ratios than transient responders who relapsed after treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes, patients with genotype 1b had higher T/B ratios in the sustained response group than in the nonsustained response groups (P = 0.001), but patients with genotype 2 had a similar distribution of T/B among the 3 response groups (not significant). These findings indicate that the physicochemical properties of HCV affect the effectiveness of interferon therapy, particularly in patients with genotype 1b.

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Significance of IgG and IgM HCV antibody secretion in vitro in patients with chronic hepatitis C: Correlation with disease activity and response to interferon-α

Cited by 12 publications

References 40 publications

Analysis of B‐lymphocyte differentiation in patients infected with hepatitis C virus

Analysis of B‐lymphocyte differentiation in patients infected with hepatitis C virus

Quantitative analysis of anti–hepatitis C virus antibody–secreting B cells in patients with chronic hepatitis C†

Differential flotation centrifugation study of hepatitis C virus and response to interferon therapy

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