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)

We analyzed primary-cultured human hepatic macrophages (HHMphi) from 12 patients with non-cirrhotic and cirrhotic livers for cell surface expression of HLA-DR antigen and interleukin-2 receptor (IL-2R). Compared to the relatively abundant HLA-DR antigen, IL-2R expression was generally low. No significant difference was observed between HLA-DR antigen expression nor IL-2 receptor expression. HHMphi from patients with serum hepatitis viral markers, however, expressed significantly more HLA-DR antigen than did HHMphi of patients without viral markers, which suggest a possible role of HHMphi as antigen-presenting cells (APC) in viral hepatitis. This direct, quantitative measurement of cell surface molecule expression on hepatic macrophages of human may provide an important clue to the pathophysiology of human liver disorders.
 ...
PMID:HLA-DR antigen and interleukin-2 receptor expression on primary-cultured human hepatic macrophages in relation to liver cirrhosis and hepatitis virus infection. 863 8

The HLA multigene family consists of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) genes, and plays a central role in the regulation of immune response. To investigate how each HLA gene and each HLA allele contribute to the human immune response, we immunized 339 healthy Japanese medical students with recombinant hepatitis B surface antigen (rHBsAg) and determined the HLA types of all vaccinated subjects at the DNA level. The anti-HBs antibody titers showed a log-normal distribution, implying that the immune response to HBsAg in humans is a multifactorial and continuous trait. A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly contributed to antibody production to HBsAg. The predicting equation of anti-HBs antibody levels for individuals with any HLA phenotype was proposed based on a multiple regression analysis. The multiple correlation coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whole HLA class I or class II loci were 0.36 or 0.44 respectively. The incorporated correlation coefficient of the presence of all HLA gene families with antibody production became 0.50, suggesting that HLA class I and class II loci within the HLA multigene family are dynamically involved in regulation of the immune response to HBsAg.
 ...
PMID:Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans. 867 39

It is widely believed that the hepatitis B virus (HBV) is completely cleared by antiviral antibodies and specific cytotoxic T lymphocytes (CTLs) during acute viral hepatitis. We now demonstrate that traces of HBV are often detectable in the blood for many years after clinical recovery from acute hepatitis, despite the presence of serum antibodies and HBV-specific CTLs, which can be present at acute-stage levels. The strength of the CTL response to HBV following clinical recovery correlates with persistence of HBV DNA. It is of particular interest that HBV-specific CTLs from patients studied up to 23 years after clinical and serological recovery expressed activation markers (HLA-DR, CD69) indicating recent contact with antigen. These results suggest that sterilizing immunity to HBV frequently fails to occur after recovery from acute hepatitis and that traces of virus can maintain the CTL response for decades following clinical recovery, apparently creating a negative feedback loop that keeps the virus under control, perhaps for life.
 ...
PMID:The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. 883 8

Recurrence of hepatitis B virus (HBV) in the graft is the major problem for patients with chronic HBV infection undergoing liver transplantation, which could be potentiated by the immunosuppression. In the present study, we used lymphocytes and hepatocytes isolated from patients with chronic HBV infection to investigate in vitro the effects of FK506 with and without methylprednisolone (25 ng/mL) on mitogen-induced lymphocyte proliferation, T-cell activation marker expression, and HBV replication in human hepatocytes. Increasing concentrations of FK506 (0.1, 0.5, and 5 ng/mL) resulted in a dose-dependent inhibition of lymphocyte proliferation with a reduction of the stimulation index by 9.2%, 39.0%, and 55.1%, respectively, with no difference between 25 chronic HBV carriers and normal controls. Methylprednisolone alone had no effect but potentiated the inhibitory effect of all three FK506 concentrations, such that the stimulation index was decreased by 20%, 56.2%, and 65.7%, respectively. FK506 (0.5 ng/ mL) reduced both the percentage of interleukin-2 receptor expressing T cells and the cell surface density of this receptor by 7.1% and 8.7% (P < .01), whereas it only reduced the proportion of HLA-DR expressing T cells by 6.8%. FK506 did not change significantly the intracellular HBV DNA or the hepatic expression of hepatitis B surface antigen (HBsAg) in short-term culture of human hepatocytes, whereas methylprednisolone increased the percentage of HBsAg-positive hepatocytes in all 5 patients with active viral replication. These results indicate that the effects of FK506 on T-cell activation in chronic HBV carriers are identical to normal subjects, resulting in marked suppression of T-lymphocyte function but only modest reduction in the expression of cell surface activation markers. The drug showed no direct stimulatory effect on viral replication, suggesting that FK506 can be a useful, steroid-sparing immunosuppressive agent for liver graft recipients with chronic HBV infection.
 ...
PMID:FK506 in liver transplantation for chronic hepatitis B: in vitro studies on lymphocyte activation and virus replication. 934 13

The aims of this prospective study were to assess the frequency of serological markers of autoimmunity and cryoglobulins in renal transplant (RT) patients presenting with chronic hepatitis C, and to correlate them with serum alanine aminotransferase (ALT) levels, hepatitis C virus (HCV) genotypes and viremia, and HLA-DR phenotypes. Three groups of patients were studied: group I comprised 74 HCV + ve RT patients; group II, 33 HCV-ve RT patients, and group III, 13 HCV-ve/hepatitis B virus (HBV)-positive RT patients. The three groups did not differ significantly according to their mean age, sex ratio and baseline immunosuppression. Serum specimens of these patients were tested for complement (hemolytic activity (CH50), C3, C4 and properdin factor B (PFB) components, rheumatoid factor (RF), immunoglobulin patterns, circulating immune complexes, and autoantibodies including antinuclear (ANA), anti-smooth muscle (ASMA), antimitochondrial, antithyroid microsomal (ATM), antithyroglobulin (ATG) and anti-LKM1 autoantibodies. We also looked for the presence of cryoglobulins in groups I and III. Cryoglobulinemia of type II was present in 2 patients of group I (2.7%) which was associated in 1 case with de novo membranoproliferative glomerulonephritis but was not found in any of the patients of group III. RF (> 40U/ml) were more frequently observed in groups I (55.4%) and III (46%) than in group II (20.6%), although the difference was not statistically significant (p = 0.06). Oligoclonal or monoclonal serum immunoglobulin patterns were present in 16.2% of the patients in group I, 15.4% in group III and only 3.3% in group II (p = 0.07). There was no significant difference between the prevalence of at least one autoantibody in the three groups (ranging from 38.5 to 50%), and neither was the frequency of ANA (23-36.6%), even at a high titer i.e. above 1:320, or ASMA (13.5-23%) significantly different. Conversely, tissue-specific autoantibodies, i.e. ATM, ATG and anti-LKM1, were only observed in HCV+ve patients. CH50, C3, C4 and PFB levels were significantly lower in group I than in group II, although values below the normal ranges were observed only for CH50 and C3 and were mostly found in the HCV+ve RT patients. Circulating immune complexes detected by nephelometry were at similar levels in the three groups, within the normal ranges. The occurrence of at least one autoantibody and/or the presence of RF > 40 U/ml did not correlate with either serum ALT levels or a given HLA-DR phenotype in any of the three groups, nor did they correlate with HCV genotype or HCV viremia in group I. In conclusion, this study shows that contrary to HCV+ve immunocompetent patients, HCV+ve RT patients rarely present with cryoglobulinemia and have the same frequency of non-organ-specific autoantibodies as HCV-ve RT patients. Conversely, antithyroid autoantibodies are only observed in the former group. Finally, serological markers of autoimmunity are not related to serum ALT levels, HLA-DR phenotype, HCV viremia or HCV genotype in HCV+ve RT patients.
 ...
PMID:Serological markers of autoimmunity in renal transplant patients with chronic hepatitis C. 948 39

Dysregulation of T-cell receptor (TCR) alphabeta bearing lymphocytes and an increase in Vdelta1+ gammadelta T cells are typical features of HIV-1 infection. However, the role of gammadelta T cells remains unclear. Therefore, peripheral blood mononuclear cells (PBMC) of 103 HIV-1-infected patients were investigated with respect to expression of Vdelta1. These results were compared to the Vdelta1 expression of bone marrow mononuclear cells (BMMC). In contrast to healthy controls, Vdelta1+ cells dominated among both PBMC and BMMC in HIV-1-infected patients. Analysis of the coexpression of CD25, CD8, HLA-DR and CD45RO revealed a high prevalence of Vdelta1/CD45RO and Vdelta1/HLA-DR double-positive PBMC only in HIV-1-infected patients but not in healthy donors. Furthermore, analysis of the gammadelta TCR repertoire in patients infected with hepatitis B virus, hepatitis C virus, herpes simplex virus (HSV)-1 and HSV-2 showed that the selective enhancement of Vdelta1+ cells was restricted to HIV infection and not observed in other virus diseases. Our data provide further support for the involvement of gammadelta T cells in immunosuppression and progression of HIV infection.
 ...
PMID:Increase in Vdelta1+ gammadelta T cells in the peripheral blood and bone marrow as a selective feature of HIV-1 but not other virus infections. 953 41

To characterize the immunological populations associated with different stages of chronic infection with hepatitis B virus (HBV), we performed flow cytometric analyses on the peripheral blood leucocytes of 29 patients with various forms of chronic hepatitis B. The clinical spectrum of the patients ranged from asymptomatic infections, in the presence of high virus production, to intermittent or recurrent exacerbations of liver injury alternating with relatively normal liver function. Patients with partial resolution of disease who experienced an initial acute flare followed by prolonged seroconversion showed decreased percentages of CD3+ cells during the seroconversion phase when levels of serum alanine transferase (ALT) had normalized. These CD3+ cells were predominantly CD4+ cells bearing the alpha beta+ T-cell receptor (TCR). In addition, we saw an increase in CD4+ and CD8+ cells bearing the gamma delta TCR in those patients who had seroconverted. No significant differences were seen between any of the groups with respect to percentage of cells with a naive (CD45RA) or memory (CD45RO) phenotype, or of cells displaying the activation markers CD38, HLA-DR or CD57. Longitudinal analyses of 15 patients failed to show any consistent pattern of changes in the immunophenotypic profile during acute flares and their resolution. Our results indicate that the turnover of circulating T lymphocytes during the apparent quiescent phase of chronic infections is higher than that during acute exacerbations, suggesting an active immunosurveillance role of T-cell subpopulations in maintaining low virus levels during seroconversion.
 ...
PMID:Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus. 957 32

The objective was to evaluate the rationale for liver needle biopsy versus blood liver functional tests in monitoring the incidence of hepatotoxicity in Egyptian rheumatoid arthritic patients treated with gold compounds. Forty patients (12 males, 28 females) were randomly selected out of 258 Egyptian rheumatoid arthritic patients treated with sodium auro-thiomalate during the past 4 years. The minimum duration of treatment was 40 weeks. The methods used were firstly, liver function tests (serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total serum bilirubin and total serum albumin) before, weekly during and after administration of sodium auro-thiomalate. Secondly, a needle liver biopsy was conducted by using the tru-cut needle. Then liver histology was graded according to Roenigk for grading liver toxicity. Viral hepatitis markers (hepatitis B surface antigen, anti-hepatitis C virus were done for monitoring viral hepatitis. Finally, the liver tissue contents of heavy metals were counted in the cases that showed grade IIIB histological changes. The results showed that none of the studied cases developed any clinically significant liver disease during the course of chrysotherapy. Blood liver function tests were of normal value throughout the course of drug administration. According to Roenigk grading, 20 patients (50%) showed grade I liver changes, and the other 20 patients showed liver changes of grades II and III (four grade II, eight grade IIIA, and another eight grade IIIB). None of the patients showed grade IV liver changes. It was concluded that blood liver tests are not the most sensitive methods to detect hepatotoxicity in gold-receiving Egyptian rheumatoid arthritic patients. Needle liver biopsy is not superior in detecting liver toxicity, compared with routine laboratory liver function tests, because of its complications. Rheumatoid arthritic patients with a potential risk of clinically significant liver disease should not be exposed to the risk of gold salt therapy. Pretreatment HLA-DR genetic typing may be a good detector for rheumatoid arthritic patients with potential risk of hepatotoxicity.
 ...
PMID:Liver toxicity profile in gold-treated Egyptian rheumatoid arthritis patients. 960 32

The mechanism underlying the impaired immune response to hepatitis B vaccines in up to 10% of healthy subjects is not known. An increased incidence of poor responsiveness in subjects with HLA-DR3+ or -DR7+ haplotypes has been documented, suggesting that HLA-DR-linked genes may regulate the human response to hepatitis B surface antigen. However, not all HLA-DR3+ and/or -DR7+ individuals are poor responders, and subjects with identical HLA-DR haplotypes sometimes display totally divergent antibody responses to vaccination. HLA class II DNA typing was performed in well and poorly responding hepatitis B vaccine recipients and we analyzed the role of the single HLA-DR, -DP, and -DQ molecules and of their associated (interaction) haplotypes in the response to hepatitis B vaccination. Statistical analysis revealed that HLA-DRB1*010*, -DR5, -DPB1*040*, -DQB1*0301, and -DQB1*0501 were more abundant in good responders, whereas HLA-DRB1*07, -DPB1*1101, and -DQB1*020* were associated with poor response, with DQB1*020* showing the strongest association with poor responsiveness. We further investigated whether there were interactions between the HLA factors contributing to poor responsiveness. We show here that HLA-DPB1*02 was negatively associated with responsiveness when it occurred in association with haplotype DRB1*0701/DRB4*0101-DQB1*020*, and DRB4*0101 was negatively associated with responsiveness when it occurred in association with haplotype DRB1*0301/DRB3*0101-DQB1*020*. Our results indicate that the immune response to hepatitis B vaccine is largely determined by HLA-DR, -DP, and -DQ genes and that interaction between HLA molecules that are not in linkage disequilibrium contributes to poor responsiveness.
 ...
PMID:Response to hepatitis B vaccine: multiple HLA genes are involved. 969 51

A strong virus-specific CD4+ and CD8+ T lymphocyte response to hepatitis B virus (HBV) has been associated with viral clearance, but little is known about factors determining the individual's ability to mount such a T cell response. Recently a strong association between the HLA class II allele DR13 and a self-limited course of HBV infection has been described. In the present study of 33 patients with acute hepatitis B we show that individuals carrying HLA-DR13 mount a more vigorous CD4+ T cell response to HBV core (5706 ct/min (25th/75th percentile 3239 ct/min; 10,552 ct/min)) than patients without HLA-DR 13 (1365 ct/min (490 ct/min; 5334 ct/min); P = 0.006). However, peptide epitopes aa 50-69, aa 61-85, and aa 81-105 were recognized most frequently by both patient groups. Moreover, among 14 HBV core-specific CD4+ T cell clones from two patients with HLA-DR13, only one T cell clone was HLA-DR13-restricted. Our data suggest that the beneficial effect of the HLA-DR13 alleles on the outcome of HBV infection could be explained by a more vigorous HBV core-specific CD4+ T cell response, which may either be due to more proficient antigen presentation by the HLA-DR13 molecules themselves or a linked polymorphism in a neighbouring immunoregulatory gene.
 ...
PMID:A vigorous virus-specific CD4+ T cell response may contribute to the association of HLA-DR13 with viral clearance in hepatitis B. 971 74


<< Previous 1 2 3 4 5 6 7 Next >>