Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly purified CD4+ T cells isolated from liver biopsies of patients with hepatitis B virus-induced CAH had a strong cytotoxic activity and were comprised of a substantial number of cells (25%-40%) expressing CD56 surface marker. These cells were absent in CD4+ T cells from the peripheral blood of CAH patients or normal controls and these suspensions did not have cytotoxic activity. CD4+CD56+ T cells were further characterized by studies at the clonal level. A total of 71 hepatitis B envelope antigen-specific CD4+ T cell clones was investigated (23 from liver biopsies, 48 from peripheral blood of patients or normal vaccinated individuals). A total of 16 out of 23 (69.5%) of the clones from liver biopsies, but only 4.1% (2 out of 48) of those from PBLs, expressed CD56. A clone was defined as CD56+ when 40% or more of the cells expressed the marker. Production of TNF-alpha, IL-4, IL-5, IL-2, and IFN-gamma was investigated in 15 CD4+CD56+ and in 18 CD4+CD56- T cell clones, which shared the same HLA restriction element (DR2w15) and the same fine specificity (peptide 193-207 of the S region). All of the clones from the two groups released TNF-alpha and IL-2. However, all of the CD4+CD56+ T cell clones produced IFN-gamma but not IL-4 and IL-5 (Th1-like cell clones). Fourteen of the CD4+CD56- clones released IFN-gamma, IL-4, and IL-5 (Th0-like cell clones); three produced IL-4 and IL-5 but not IFN-gamma (Th2-like cell clones); and only one had a Th1 cytokine secretion profile. Cell fractionating studies within single CD4+CD56+ T cell clones showed that cells expressing high density CD56 had a stronger cytotoxic activity and produced higher levels of IFN-gamma than cells with low density CD56, thus further supporting a correlation between CD56 expression and cell functions. The results indicate that: 1) in CAH patients, cytotoxic CD4+ T cells with a Th1 cytokine secretion profile are compartmentalized in the liver, 2) these cells may be identified by the expression of CD56, 3) the expansion of these cells may be facilitated by antigenic stimulation within the inflammatory environment of the liver, and 4) CD4+CD56+ cells may play a pathogenetic role in hepatitis B virus infection.
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PMID:Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with Hepatitis B virus. 751 37

The presence of hepatitis B surface protein (HBs) and hepatitis B core protein (HBc) was investigated, by flow cytometry, on the surface of peripheral mononuclear cells (PBMC) from cells of the following phenotype: CD3 (T lymphocytes), CD4 (T helper/ inducer), CD8 (T cytotoxic/suppressor), CD19 (B lymphocytes) and CD56 [natural killer (NK) cells] among eight patients suffering from chronic hepatitis B and five healthy HBV-negative subjects. This study demonstrated the presence of HBsAg and HBcAg on the lymphocyte surface for most of the patients. The mean percentage of labelled cells was 17% for HBsAg and 15% for HBcAg. Among the different lymphocyte subsets only B lymphocytes and the NK cells expressed HBsAg for 57% and 26% of cells, respectively. Similarly HBcAg was also detected among CD19 and CD56 cells only. Polymerase chain reaction (PCR) was used to search for the presence of hepatitis B virus (HBV) DNA and RNA in PBMC, using primers located in the S gene. HBV DNA was detected with variable intensity in the CD3, CD4, CD19 and CD56 subsets following their separation with a cell sorter. For HBV RNA the signal obtained after PCR and Southern blotting was higher for CD56 and CD19 cells than for CD3 cells and undetectable for CD4 cells. This study demonstrates that replication and transcription of the HBV can occur in CD19- and CD56-positive cells. Positive signals in CD3 cells may be due to contamination of this subpopulation by NK cells.
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PMID:Selective detection of human hepatitis B virus surface and core antigens in peripheral blood mononuclear cell subsets by flow cytometry. 879 May 58

BACKGROUND AND AIM: Thymosin-alpha1 (T-alpha1) influences T-cell maturation, production of Th1-type cytokines, and activity of NK cell-mediated cytotoxicity. The aim of this study is to evaluate the types of lymphocytes that contribute to the reduction in viral load in patients with chronic hepatitis B (CHB) following T-alpha1 treatment. METHODS: Seven patients with CHB were treated with 1.2 mg of T-alpha1 for 24 weeks. Peripheral blood lymphocytes (PBL) and intrahepatic lymphocytes were analyzed by flow cytometry. Serum cytokines (IL-4 and IFN-gamma) were measured by ELISA. RESULTS: Forty-eight weeks after T-alpha1 treatment, two patients (28.6%) showed normalized alanine aminotransferase and decreased HBV-DNA to undetectable level from serum. The histology activity index score significantly decreased (P<0.05). Although elevated serum interferon (IFN)-gamma was not observed, IFN-gamma producing Th1-type CD4(+) PBL appeared to be increased. CD56(+) natural killer T (NKT) cells in PBL did not increase, these cells in the liver remained significantly augmented even at the end of treatment (P<0.05). CD57(+) NKT cells slightly increased and the ratio of CD4(+) T/CD8(+) T cells decreased in the liver. T-alpha1 did not influence either double-positive CD4(+)8(+) T or double-negative CD4(-)8(-) cell subsets. CONCLUSION: NKT cells and CD8(+) cytotoxic T lymphocytes augmented in the liver by T-alpha1 may eliminate hepatitis B virus infected hepatocytes.
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PMID:Thymosin-alpha1 increases intrahepatic NKT cells and CTLs in patients with chronic hepatitis B. 1247 32

The prevention of hepatitis B is important, since it is responsible for significant morbidity and mortality around the world. Unfortunately, hepatitis B vaccine does not always induce protective immunity. The lack of immune response to vaccine (non-responders) can depend on individual characteristics. The objective of this study was to correlate the CD26/DPPIV cellular expression and DPPIV serum activity with HBV vaccine response and its possible role as an indicator of immune competence acquisition. We also determined the cellular expression of CD3, CD19, CD56 and CD25 in peripheral blood T lymphocytes. Blood samples were obtained from 28 healthy human volunteers who were enrolled with a vaccination program. There were "responders" (RM = 13) and "non-responders" (NRM = 15), after vaccination. The lymphocyte populations were identified by flow cytometry. DPPIV serum activity was measured fluorimetrically. CD26 expression in responders (55.9 +/- 7.7%) versus in non-responders (51.9 +/- 7.0%) did not show a significant difference. The DPPIV serum activity in responders compared to in non-responder subgroup (59.9 +/- 8.4/50.3 +/- 10.6U/L) showed, however, a significant difference (P < 0.05). The expression of CD3, CD19 and CD56 on peripheral lymphocytes was similar between responders and non-responders. The expression of CD3CD26 (52.2 +/- 8.6%) and CD3CD25 (10.9 +/- 3.8%) in responders versus the expression of CD3CD26 (48.0 +/- 5.7%) and CD3CD25 (8 +/- 4.6%) in non-responders did not show statistically significant difference. CD25 referred as a marker of T lymphocyte activation was increased in responders (15.8 +/- 4.5%) versus in non-responders (10.1 +/- 4.8%), showing a significant difference (P = 0.003). It was, however, impossible to demonstrate an increase in CD3CD25 and CD3CD26 in the responder subgroup. This suggests that different lymphocyte subsets other than T cells are implicated in the response to hepatitis B vaccination.
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PMID:CD26/DPPIV and response to hepatitis B vaccination. 1556 11

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.
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PMID:Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A. 1685 14

The Caribbean relies on normal lymphocyte subsets ranges established in other geographical locations and from different racial ethnic groups for the basis of the clinical management of HIV and AIDS with Highly Active Anti Retroviral Therapy (HAART). Normal ranges of these parameters have not been previously established in an Afro-Caribbean population. So we set out to determine how the normal lymphocyte subset ranges compare to those reported in other, races and geographical locations. A prospective study was done on 112 healthy Afro-Caribbean clients who attended the Blood Collection Unit, Queen Elizabeth Hospital, Barbados from July 15th to November 12th 2004. Analysis for lymphocyte subsets was done by flow cytometry, which allows simultaneous identification and enumeration of total T Helper, cytotoxic T, natural killer and B lymphocyte cells. HIV-1, Hepatitis B and C, HTLV-1 and full blood count test were done as part of the normal screening routine of all blood donors. Absolute white blood cell counts and percentage lymphocytes for males and females were not significantly different, and the absolute and percentage of the T-Helper CD4 positive lymphocyte cells were not significantly higher in females than in males. Absolute Cytotoxic T cell CD8 positive lymphocyte cells were higher in males than in females. CD56 Natural Killer cells absolute and percentage counts were higher in males than females however CD19 B Lympocyte absolute and percentage counts were not different between the two sexes in this sample population. Compared to published normal ranges published by the WHO and CDC, there were no significantly differences observed in any of the lymphocyte subsets. These finding are very similar to what has been reported in previous studies. We conclude that WHO/CDC recommendations established for the treatment and monitoring of HIV/AIDS patients based on CD4 levels can be safely utilized in our population.
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PMID:Characteristics of lymphocyte subsets in a normal Afro-Caribbean population and the implications in HIV management. 1805 Jul 83

Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, >90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.
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PMID:The properties of tumor-initiating cells from a hepatocellular carcinoma patient's primary and recurrent tumor. 1989 2

Sixty-six B-cell lymphoma patients were treated with a CHOP-based chemotherapy containing rituximab (R-CHOP-like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty-five patients (83.3%) underwent six cycles of the R-CHOP-like regimen. CD19(+) and CD20(+) cells were completely eliminated from the peripheral blood after one cycle of the R-CHOP-like regimen; they were detected again 6 months after the therapy. One year after the therapy, B-cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3(+) , CD8(+) and CD56(+) cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4(+) T-cells were at their lowest after six cycles of the regimen and recovered slowly for 2 years after the therapy; however, their numbers were still lower than that at diagnosis. Immunoglobulins decreased over six cycles of the R-CHOP-like regimen and then recovered gradually for 2 years after the therapy. The percentage of IgG, IgA and IgM 2 years after the therapy compared with those at diagnosis was 93.9%, 90.1%, 76.3%, respectively. Twelve infectious complications occurred which consisted of three febrile neutropenia, three Herpes Zoster, two tympanitis, two Pneumocystis jiroveci pneumonia and two hepatitis B virus reactivation. B-cells required 1 year and CD4(+) T-cells and immunoglobulins needed 2 years to recover after the therapy.
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PMID:Immune reconstitution of B-cell lymphoma patients receiving CHOP-based chemotherapy containing rituximab. 2055 73

Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack of understanding of pathogenesis as well as a lack of effective treatments. Signals from the inhibitory receptor programmed death-1 (PD-1) have been demonstrated to be involved in regulating the pathogenesis of infectious diseases. However, the expression of PD-1 and its ligands in HBV-ACLF patients has yet to be evaluated. In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-ACLF as well as chronic hepatitis B (CHB) patients were analyzed by immunohistochemistry. The results showed that all three molecules were observed in the HBV-ACLF samples and their levels were significantly higher than they were in CHB. Immunofluorescence double-staining showed that PD-1 was found on CD3(+), CD8(+) T cells, CD56(+) NK cells, CD68(+) macrophages, CK-18(+) epithelial cells, and CD16(+) monocytes. The PD-L1 expression was observed on all cell types detected and the PD-L2 was chiefly on CK-18(+) epithelial cells and CD31(+) endothelial cells. Interestingly, high levels of virus-induced procoagulant molecule fibrinogen-like protein 2 (FGL2) were observed in liver sections from HBV-ACLF, and PD-L1 and PD-L2 expression was also observed on FGL2(+) cells in these patients. Our combined results suggest that the expression of PD-L1 and PD-L2 may be biomarkers to identify and diagnose ACLF, and a clear understanding of their functional roles should further elucidate the pathogenesis of this disease.
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PMID:Intrahepatic expression of programmed death-1 and its ligands in patients with HBV-related acute-on-chronic liver failure. 2289 98

Chronic infection with hepatitis B virus (HBV) is associated with impairment of T and NK cell immunity. This study was aimed at investigating the impact of treatment with telbivudine (LDT) on T and NK cell immunity in patients with chronic hepatitis B (CHB). A total of 54 CHB patients and 30 healthy controls (HC) were recruited. Individual patients were treated orally with 600 mg LDT daily for 13 months. The serum HBV DNA loads, the levels of the HBV-related biomarkers alanine aminotransferase (ALT) and aspartate transaminase (AST), and the numbers of different subsets of peripheral T and NK cells in subjects were measured before and longitudinally after LDT treatment. Following treatment with LDT, the serum HBV DNA loads and the percentages of HBsAg- or HBeAg-seropositive cases were gradually reduced, accompanied by decreased levels of serum ALT and AST. In comparison with the HC, fewer CD3(-) CD56(+) and CD244(+) NK cells and CD3(+) CD8(+) T cells, lower frequencies of cytokine(+) CD4(+) T cells, and more CD3(+) CD4(+), CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells were detected in CHB patients. Treatment with LDT increased the numbers of NK and CD8(+) cells and the frequencies of cytokine(+) CD4(+) T cells but reduced the numbers of CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells in CHB patients. The frequencies of cytokine(+) CD4(+) T cells were negatively associated with the levels of serum HBV DNA, ALT, and AST. Thus, treatment with LDT inhibits HBV replication, modulates T and NK cell immunity, and improves liver function in Chinese patients with CHB.
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PMID:Treatment with telbivudine positively regulates antiviral immune profiles in Chinese patients with chronic hepatitis B. 2327 69


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