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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 127 records · Page 7Linked to original sources
PubMed1997

Antineutrophil nuclear antibodies (ANNA) in primary biliary cirrhosis: their prevalence and antigen specificity.

Antineutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies first associated with Wegener's granulomatosis (WG). In autoimmune liver diseases, ANCA have been described recently in patients with primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Controversy exists about the prevalence and specificity of ANCA in patients with autoimmune liver diseases. The purpose of this study was first to assess the prevalence of antineutrophil antibodies in patients with primary biliary cirrhosis and second to identify possible target antigens of antineutrophil antibodies. Sera from 33 patients with PBC, 75 patients with AIH, 16 patients with PSC, 90 control sera (chronic hepatitis B, chronic hepatitis C, alcoholic liver cirrhosis, systemic lupus erythematosus) and sera from healthy blood donors were enrolled in the present study. ANA and ANCA were detected using standard protocols, antibodies against the nuclear antigen SP100 were detected by ELISA with recombinant antigen, antibodies against neutrophil alpha-granules were detected by ELISA. P-ANCA were found in two of 33 PBC sera, both patients presented with PBC/AIH overlap syndrome. In six of 33 (18%) PBC sera a nuclear dot like immunofluorescence pattern (antineutrophil nuclear antibodies, ANNA) was observed. These dots were small in size and located all over the nucleus, the anti-SP100 fluorescence. This result was confirmed by IFT on HEp-2 cells and by ELISA. High tier antibodies against SP100 were found to be specific for patients with PBC. Comparing the IFT results on HEp-2 cells and human neutrophils, we found an excellent correlation (Spearman's rank correlation coefficient = 0.968, P < 0.001). ANCA were detected in AIH type-1 (75%), SLA-positive AIH (36%) and PSC (63%). AIH type-2 was found to be ANCA negative. All PSC contained no antibodies against neutrophil alpha-granules. Our results show: 1. P-ANCA in patients with PBC indicate a PBC/AIH overlap syndrome; 2. ANNA in patients with PBC are mostly directed against SP100; 3. neutrophil granule components are not the ANCA specific antigens in patients with PSC.

Adult↗
PubMed1997

Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha.

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.

Adult↗
PubMed1997

Coombs-negative severe hemolysis associated with hepatitis A.

Mild anemia can occasionally be observed during viral hepatitis, but severe hemolysis has previously only been reported in a few patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive acute hemolysis associated with an acute hepatitis A in a 39-year-old woman in the absence of G6PD-deficiency. The patient was also suffering from mild rheumatoid arthritis. All known factors responsible for hemolysis were ruled out. Although tests for autoimmune hemolytic anemia were negative the patient made a dramatic recovery after treatment with corticosteroids, suggesting an immune mediated mechanism nonetheless.

Adult↗
PubMed1997

Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis--report of three cases.

Autoimmune hepatitis is a chronic inflammatory disorder of the liver with a fluctuating course, which often requires long-term immunosuppressive therapy in order to prevent fibrosis to the liver. The mainstay of immunosuppressive therapy is the use of corticosteroids, usually in conjunction with azathioprine. However, in a subgroup of patients with severe side effects or intolerance of standard therapy there is a need for alternative immunosuppressive agents. We describe the successful long-term treatment of three patients with severe autoimmune hepatitis with an immunosuppressive regimen consisting of cyclophosphamide and corticosteroids. In the reported patients we were able to induce remission with cyclophosphamide in a dose of 1-1.5 mg/kg bodyweight in combination with a tapering dose of corticosteroids beginning with 1 mg/kg bodyweight. After induction we were able to maintain histology proven remission with low doses of corticosteroids (2.5-10 mg/day) together with 50 mg of cyclophosphamide every other day. With this dose of cyclophosphamide we have neither observed relapse of autoimmune hepatitis nor severe side effects in a cumulative observation period of more than twelve years in the three patients. As a consequence of our favourable experience with cyclophosphamide in the reported cases, we propose cyclophosphamide as an alternative to azathioprine in cases of autoimmune hepatitis with severe side effects of intolerance of standard therapy.

Adult↗
PubMed1996

[Duplex sonographic studies on the pathogenesis of splenic hemodynamics in liver cirrhosis].

AIM OF STUDY: The haemodynamic role of the spleen in portal hypertension remains unclear. Duplex sonography was undertaken prospectively to discover the relationship of splenomegaly and splenic vein flow to type and severity of liver cirrhosis and portal vein flow, as well as to the degree of oesophageal varices. PATIENTS AND METHODS: 89 patients (54 men, 35 women; mean age 52 [26-81] years), diagnosed in the second half of 1993 as having liver cirrhosis were consecutively included in the study. In 40 patients the cirrhosis was in stage A (according to Child-Pugh classification), in 31 in stage B and in 18 in stage C. RESULTS: Portal vein flow fell significantly with increasing degree of cirrhosis (stage A: 8.29 cm/s; stage B 7.03 cm/s; stage C 5.26 cm/s; P < 0.05). Splenic vein flow differed significantly only between stages B and C (stage A: 9.22 cm/s; stage B: 9.46 cm/s; stage C: 7.87 cm/s; B vs C, P < 0.05). There was no correlation between portal vein flow, splenic vein flow, degree of splenomegaly and extent of oesophageal varices. CONCLUSION: The results may be explained by the presence of collateral circulations and by the differing pathophysiological part played by the spleen in liver cirrhosis of different aetiologies.

Adult↗
PubMed1996

Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240 bp fragment comprising the pre-core region of HBV was amplified by polymerase chain reaction (PCR). Pre-core mutants of HBV were determined by direct sequencing of these PCR products and by sequencing of PCR clones. Eight of 17 patients were infected with pre-core wildtype HBV before OLT (group A). Seven of eight patients of group A were reinfected by pre-core wildtype HBV after OLT. In one of eight patients in addition to wildtype HBV a mutant strain (nt. 1899 G-->A) was detected. Nine of 17 patients were infected with pre-core mutant HBV before OLT (group B). Six of nine patients of group B were reinfected with the same mutant population; in one, an additional pre-core mutation emerged; two patients lost pre-core mutant HBV (nt. 1896 and 1899 G-->A). In one of the latter two, a pre-core start-codon mutant (nt. 1816 G-->T), not detectable before OLT, emerged, in the other a nt. 1897 G-->A stop-codon mutant persisted. Five patients of each group were followed-up for more than 24 (25 to 58) months on immunosuppressive therapy. In all five patients of group A, pre-core wildtype of HBV persisted during long-term follow up. Two of five patients of group B were infected stably with a stop-codon HBV-mutant nt. 1896. In three patients, the nt. 1896 stop-codon mutant disappeared during immunosuppressive therapy. However, in one of the latter three, an HBV stop-codon mutant nt. 1897 persisted. In conclusion, most patients who underwent OLT for HBV-related disease were reinfected with the same virus population that existed before OLT. In rare cases, new mutants emerged after OLT or preexisting mutants were lost. During long-term follow-up on immunosuppressive therapy, in the majority of patients pre-core mutants disappeared and wildtype HBV became the predominant virus strain.

Antiviral Agents↗
PubMed1996

Role of sinusoidal endothelial cells of the liver in concanavalin A-induced hepatic injury in mice.

CD4+ T lymphocytes have been identified as being responsible for organ damage in the murine model of experimental liver injury induced by intravenous injection of concanavalin A (Con A). Liver sinusoidal endothelial cells (SEC) and Kupffer's cells (KC) are among the first cells that come into contact with lymphocytes in the liver sinusoid. We aimed to investigate the respective role of these cell populations in the initial steps of T-cell-mediated liver injury in Con A-induced hepatitis. By electron microscopy, we could show that intravenously applied Con A bound predominantly to SEC but not to KC. KC depletion by gadolinium chloride treatment of mice did not result in protection from liver injury, indicating that KCs are not primarily involved in the generation of liver injury. We could show that a CD4+ T-cell line (LNC.2) displayed selective cytotoxicity toward SEC (>50%) but not KC (12%) or fibroblasts (5%) in the presence of Con A in vitro. Microscopic observation revealed that the SEC monolayer was rapidly destroyed by LnC2 in the presence of Con A. Specificity of the Con A-induced cytotoxicity was shown by the ability of a competitive ligand, methyl-alpha-D-mannopyranoside, to reduce T-cell-mediated cytotoxicity to SEC by more than 50%. Tumor necrosis factor alpha (TNF-alpha) was produced by LnC2 in high amounts after Con A stimulation (>6 ng/mL), but antiserum to TNF-alpha did not reduce LnC2-mediated cytotoxicity toward SEC. In conclusion, we could show for the first time that liver SECs have accessory function and are selectively destroyed by CD4+ T lymphocytes in the presence of Con A. We speculate that SEC damage is an early event in T-cell-mediated liver injury recruiting T lymphocytes from the sinusoidal circulation. Loss of the SEC barrier function then exposes underlying hepatocytes to further attack by activated T lymphocytes. These results offer a model of initiating events in T-cell-mediated liver diseases, such as viral or autoimmune hepatitis, and suggest an important role for sinusoidal endothelial cells.

Animals↗
PubMed1996

Autoreactive CD4+ LKM-specific and anticlonotypic T-cell responses in LKM-1 antibody-positive autoimmune hepatitis.

Peripheral blood mononuclear cells (PBMC) of patients with autoimmune hepatitis (AIH) and controls were studied for their proliferative response to six overlapping synthetic peptides covering the 33-amino acid immunodominant region of cytochrome P450IID6, the main target antigen of LKM-1 antibody-positive type II AIH. PBMC from 8 of 8 type II AIH patients (100%), 6 of 12 LKM-1 antibody-negative type I AIH patients (50%), but only 4 of 31 patients with chronic hepatitis C (12.9%) reacted with a 23-amino acid LKM peptide and mainly with a shorter 18-amino acid LKM peptide. Follow-up showed that LKM-specific T-cell responses decreased after immunosuppression had started. Fine specificity, HLA restriction, and cytokine release of LKM-specific T cells were analyzed with 16 CD4+ peptide-specific T-cell lines and 21 CD4+ T-cell clones isolated and expanded from blood and liver tissue of six AIH patients. Activated LKM-specific T cells released interferon gamma (IFN-gamma) but no or little interleukin-4. In three AIH patients, PBMC showed specific recognition of autologous LKM-specific T cells, suggesting the presence of a regulatory T-cell network. These T cells also showed the CD4+ phenotype and secreted large amounts of IFN-gamma. Furthermore, it was assessed that the regulatory T-cell response is clonotypic. To conclude, we describe a major T-cell epitope in AIH that was recognized by Th1 helper cells isolated from blood and liver tissue. This autoreactive T-cell response correlated widely with disease activity and LKM-1 antibody status and seemed to be regulated by anticlonotypic T cells.

Adolescent↗
PubMed1996

Semiquantitative assessment of pre-core stop-codon mutant and wildtype hepatitis B virus during the course of chronic hepatitis B using a new PCR-based assay.

In most patients with chronic hepatitis B positive for antibodies (anti-HBe) to HBe antigen (HBeAg), a pre-core mutant hepatitis B virus (HBV) with a point-mutation at nt. 1896 can be isolated. Clinical significance of the mutant virus in chronic hepatitis B is not proven yet, and screening of large numbers of sera during different clinical courses of numerous patients is necessary. We therefore aimed to develop a fast and reliable assay, that allows to discriminate wildtype from nt. 1896 G-->A mutant HBV and to determine the ratio of mutant and wildtype HBV in patients' sera. A mutation specific polymerase chain reaction (ms PCR) with new primers served to distinguish nt. 1896 G-->A mutant from wildtype HBV. This msPCR proved to be more sensitive and specific than similar assays described previously. When compared to a dilution series of a cloned HBV-DNA standard, the amount of wildtype and nt. 1896 G-->A mutant HBV could be determined semiquantitatively. 10(2) to 10(7) copies of each HBV-DNA (equivalent to 10(5) to 10(10) copies of HBV-DNA/ml patients' serum) could be amplified with steadily increasing signals. MsPCR proved to be specific as 10(7) copies did not give an amplification signal if they did not match the respective primer pair used. In a mixed population of mutant and wildtype virus, msPCR allows to detect even a low amount of the minor HBV strain (0.1-0.01%, of the viral population) and to determine the ratio of wildtype and mutant HBV. MsPCR is as fast and convenient to perform as an unmodified PCR. It requires careful performance to avoid contamination but no specific equipment. Clinical usefulness of msPCR was demonstrated when the ratio of wildtype to mutant HBV was determined in 86 sera collected during 3 to 7.5 years follow up of 9 patients suffering from anti-HBe positive chronic hepatitis B. We conclude that this assay conveniently allows to study patients with chronic hepatitis B in order to detect and follow-up the emergence of pre-core stop-codon mutant HBV in correlation to the clinical course.

Chronic Disease↗
PubMed1996

The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha.

BACKGROUND/AIM: Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients. METHODS: Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes. RESULTS: Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome. CONCLUSION: Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.

Adult↗
PubMed1996

Clinical evaluation of a single reaction, diagnostic polymerase chain reaction assay for the detection of hepatitis C virus RNA.

BACKGROUND/AIMS: In the past few years the detection of HCV-RNA by polymerase chain reaction has become a well-established diagnostic tool for patients with chronic hepatitis C. However, the lack of reproducible results between laboratories and the relatively high proportion of false-positive results, has indicated the need for a standardized and reliable polymerase chain reaction assay. In the present study we have analyzed the performance of a commercial, HCV-RNA polymerase chain reaction assay based on a single, combined reverse transcription and amplification reaction and on the use of Uracil-N-glycosilase to prevent carry-over contamination (Amplicor HCV, Roche Molecular Systems). METHODS: In this assay the amplification products are detected in microwell plates using biotinylated primer and the HRP avidin colorimetric system. Serum samples collected from 446 patients, including 181 with chronic active hepatitis C, 50 with autoimmune chronic hepatitis, 117 in hemodialysis, 30 asymptomatic carriers of anti-HCV and 68 with indeterminate serology (RIBA indeterminate results), as well as from 121 controls were tested with the commercial, single-step assay and with nested polymerase chain reaction. Both techniques use primers located within the 5' non-coding region of the HCV genome. RESULTS: In all cases a good concordance was observed between the commercial, single-step assay and nested polymerase chain reaction which, for patients with chronic active hepatitis, showed a sensitivity and specificity of 100% and 99.3% for the former and of 98.8% and 100% for the latter, when compared to clinical diagnosis taken as the gold standard. Most of the 11 discordant samples were seen in the group of RIBA-indeterminate cases and in patients with chronic active hepatitis C. Further analysis of these cases, based on repeat testing and clinical data showed that 64% and 36% of the discrepancies were due, respectively, to nested polymerase chain reaction and Amplicor inconsistent reactions. In hemodialyzed patients, patients with autoimmune hepatitis and asymptomatic carriers of anti-HCV, both assays produced results which were consistent with the clinical diagnosis. In the former group, polymerase chain reaction was able to identify the presence of active viral replication in some antibody negative samples. CONCLUSIONS: Taken together, these results indicate that the commercial, single-step polymerase chain reaction assay has the same clinical sensitivity and specificity as nested polymerase chain reaction and that, because of its simplified procedures and fast turn-around time, it may be a valuable test for routine diagnostic applications.

Hepacivirus↗
PubMed1996

Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis.

BACKGROUND/AIMS: Autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis are chronic liver diseases with probable autoimmune background. Overlapping features have been described for primary biliary cirrhosis and autoimmune hepatitis. In contrast, there have been only a few case reports on an overlap of autoimmune hepatitis and primary sclerosing cholangitis. METHODS: We describe three male patients with clinical and histological overlapping features of primary sclerosing cholangitis and autoimmune hepatitis. RESULTS: All initially asymptomatic patients had elevated levels of aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and IgG. Anti-nuclear antibodies and/or smooth muscle antibodies were positive and anti-neutrophil cytoplasmic antibodies were detected in all patients. Retrograde endoscopic cholangiography showed bile-duct strictures characteristic for primary sclerosing cholangitis. Histopathology showed necro-inflammatory activity of portal tracts with bridging necrosis in all patients at the time of first diagnosis. Aminotransferase levels and the necro-inflammatory activity responded well to immunosuppressive treatment. Predominant periductular fibrosis as a typical histopathological feature of primary sclerosing cirrhosis was seen to develop in all patients. Cholestatic serum parameters remained elevated and periductular fibrosis as endoscopic bile duct changes progressed despite immunosuppression. CONCLUSIONS: We suggest that these patients present an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis as they fulfill the diagnostic criteria for both conditions.

Adolescent↗
PubMed1996

Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases.

BACKGROUND/AIMS: Antinuclear antibodies (ANA) are a diagnostic hallmark of various autoimmune diseases and also of autoimmune hepatitis type 1. The designation ANA describes a heterogeneous group of autoantibodies. In liver diseases, only a few nuclear target antigens have been molecularly identified and characterized. Cyclins play a central role in cell cycle regulation, DNA transcription, and cell proliferation. Cyclin A was also identified as an integration site of the hepatitis B virus in a patient with hepatocellular carcinoma. In this study we identify cyclin A as a novel nuclear target protein of ANA. METHODS: Sera of patients with autoimmune hepatitis (AIH) type 1 (n = 61), type 2 (n = 21), and type 3 (n = 39), primary biliary cirrhosis (PBC) (n = 107), rheumatic diseases (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), mixed connective tissue disease (MCTD)) (n = 42) and normal controls (n = 100) were evaluated for ANA by indirect immunofluorescence. Baculovirus-generated recombinant human cyclin A protein was used for immunoblotting to study the prevalence of anti-cyclin A autoantibodies in these sera. RESULTS: Sera of patients with AIH type 1 and rheumatic diseases had ANA detected by indirect immunofluorescence. In AIH type 1 12/61 (20%) and in rheumatic diseases 6/42 (14%) were immunoblot positive for autoantibodies against human cyclin A. In PBC, AIH type 3 and normal control sera negative for ANA by immunofluorescence, anti-cyclin A autoantibodies were present in 7-9%; in AIH type 2 and SLE they were undetectable by immunoblot. In some sera a typical cyclin A immunofluorescence was observed. Anti-cyclin A antibodies recognize a 45 and 50 kDa recombinant protein species, providing evidence for the recognition of at least two molecular epitopes. CONCLUSIONS: This study has identified cyclin A as a human autoantigen in hepatic and non-hepatic autoimmune diseases. More studies are required to evaluate the clinical and pathophysiological significance of anti-cyclin A autoantibodies. The identification of human anti-cyclin A autoantibodies may additionally become a valuable tool for studying the function and regulation of cyclin A in mammalian and human cells.

Adult↗
PubMed1996

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection.

Antibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBs-specific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBV-immunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell responses in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers. However, deficient HBs-specific T and B cell responses were observed.

Acute Disease↗
PubMed1996

Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.

BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen-presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costimulatory molecules by Northern blotting, polymerase chain reaction, and flow cytometry. RESULTS: Both cell types expressed interleukin 1 messenger RNA and could serve equally well as accessory and antigen-presenting cells. B7-2 messenger RNA and surface expression on sinusoidal endothelial cells and on Kupffer cells was shown. Antibodies to the B7 molecules inhibited antigen presentation. Addition of interleukin 10 as a regulatory cytokine secreted by Kupffer cells was suppressive. CONCLUSIONS: Sinusoidal endothelial cells carry functional B7-2 molecules and can serve as effective antigen-presenting cells. However, antigen presentation by sinusoidal endothelial cells may be locally down-regulated by interleukin 10.

Animals↗