Biomedical subjects

Niamh Nolan

Publications and source records attributed to Niamh Nolan.

4 recordsLinked to original sources

PubMed2003

Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver.

BACKGROUND/AIMS: Association of hepatitis C virus (HCV) with increased autoantibodies, mixed cryoglobulinaemia, non-Hodgkin's B-cell lymphoma and increased peripheral innate (CD5(pos)) B cells suggests a role for B-lymphocytes in the pathogenesis of HCV-infection. METHODS: Flow cytometry was used to estimate CD5(pos) B cell levels and CD81 co-expression in chronic HCV infection. Viral load was assessed using PCR. RESULTS: We demonstrate expansion of innate B cells in HCV-infected liver from patients with fibrosis score less than stage II (39%, % of total B cells, P=0.002) and end stage HCV cirrhosis (20%, P<0.05) compared with normal liver (8%). Expression of CD81, a signal transducing molecule and putative HCV receptor, was significantly increased on peripheral blood CD5(pos) B cells compared with conventional B cells (P=0.0001). Higher levels of CD81 on CD5(pos) B cells were more dramatic in the liver of HCV-infected individuals. However, no significant difference was observed in the viral load of CD5(pos)CD81(High) B cells and CD5(neg)CD81(Low) B cells. CONCLUSIONS: Increased expression of CD81 on innate B cells, a population that is expanded in the livers and peripheral blood of chronic HCV-infected patients, suggests a role in viral specific activation and clonal proliferation in chronic HCV infection.

Adult↗

PubMed2002

Comparative rates of nucleotide sequence variation in the hypervariable region of E1/E2 and the NS5b region of hepatitis C virus in patients with a spectrum of liver disease resulting from a common source of infection.

The association of the severity of liver disease and the molecular evolution of hepatitis C virus (HCV) during chronic infection remains unclear and controversial. To address this we have studied the interpatient variability in the nucleotide sequence of two regions of the HCV genome, E1/E2, which contain the hypervariable region 1 and the nonstructural NS5b region, in a cohort of Irish female patients who were all recipients of a single source of HCV genotype 1b-contaminated anti-D immunoglobulin in 1977 and 1978 and who over the subsequent 20 years developed a spectrum of liver disease. In addition, quasispecies analysis was used to evaluate intrapatient variability in the E1/E2 region in four patients with mild and four with severe disease. Phylogenetic and evolutionary rate analyses of the nucleotide sequences demonstrated that there was no significant difference between those who developed mild disease and those who had progressed to severe disease or cirrhosis. These findings suggest that other factors, either additional viral or host, may be important in the pathogenesis and clinical outcome of chronic hepatitis C virus infection.

Amino Acid Sequence↗

PubMed2002

Decrease in hepatic CD56(+) T cells and V alpha 24(+) natural killer T cells in chronic hepatitis C viral infection.

BACKGROUND/AIMS: The intrahepatic immune system is likely to play a key role in determining the outcome of hepatitis C virus (HCV) infection. The hepatic lymphocyte repertoire is characterised by high CD8/CD4 T cell ratios and large numbers of gamma delta T cells, natural killer (NK) cells, NK T cells and NK receptor-positive T cells. It is not known which of these populations contribute to immunity against HCV or immune pathology. METHODS: To explore the relative contributions of lymphocyte subpopulations, we have compared the intrahepatic lymphocyte repertoires and cytokine expression in 13 patients with mild chronic hepatitis C infection, 14 with end-stage hepatitis C cirrhosis and five histologically normal livers by flow cytometry and immunohistochemistry. RESULTS: CD4(+) T cells bearing alpha beta T cell receptors (TCR) were significantly expanded in livers with chronic HCV infection while CD56(+) alpha beta T cells and V alpha 24 TCR-positive T cells were significantly depleted. Expanded CD4(+)T cells were predominantly Th1 cells, producing interferon-gamma but not interleukin-4. CONCLUSIONS: Failure to resolve HCV infection may be due to deficient innate and/or memory immune responses, while Th1 cells may mediate immune pathology.

Adult↗

PubMed2002

Mast cell hyperplasia in chronic rejection after liver transplantation.

The pathogenesis of chronic hepatic allograft rejection is poorly understood. Recent studies suggested that hepatic mast cells may be involved in the pathogenesis of chronic cholestatic liver disease. Because chronic rejection after liver transplantation is predominantly a cholestatic process, the aim of this study is to determine whether hepatic mast cells are involved in its pathogenesis. Biopsy specimens from (1) normal livers (n = 5), (2) transplanted livers with end-stage chronic rejection (n = 8), and (3) transplanted livers with acute cellular rejection (mild, n = 7; moderate, n = 5; severe, n = 7) were studied. Biopsy specimens were stained immunohistochemically for mast cells with human antitryptase antibody. Mast cell density was significantly increased in the chronic-rejection group (4.9 +/- 0.6/mm2) compared with controls (2.9 +/- 0.5/mm2; P <.05). The percentage of portal tracts containing mast cells was significantly greater in chronic-rejection (89% +/- 8%) than control biopsy specimens (69% +/- 5%; P <.05), as was the average number of mast cells per portal tract (5.4 +/- 0.9 v 1.9 +/- 0.4 cells; P <.01). In chronic rejection, tissue mast cells frequently were seen surrounding damaged bile ducts in inflamed portal tracts. Neither mast cell density nor distribution was significantly different from controls in posttransplantation biopsy specimens with acute cellular rejection of mild, moderate, or severe degree. The finding of mast cells infiltrating portal tracts and surrounding damaged bile ducts in chronic rejection suggests that hepatic mast cells may be important effector cells in the pathogenesis of chronic rejection.

Adolescent↗