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Lee S.,Royal Perth Hospital | Lee S.,University of Western Australia | Hammond T.,University of Western Australia | Watson M.W.,Center for Clinical Immunology and Biomedical Statistics | And 5 more authors.
Clinical and Experimental Immunology | Year: 2010

The proportions and activation status of T cells may influence responses to hepatitis C virus (HCV) and treatment outcome in patients receiving pegylated interferon (IFN)-α/ribavirin therapy. We confirmed that IFN-γ enzyme-linked immunospot (ELISPOT) responses to HCV are poor in HCV patients and showed that responses to HCV and cytomegalovirus (CMV) antigens decrease during therapy. This was most apparent in patients with sustained virological response (SVR). Baseline frequencies of CD4+ effector memory (TEM) T cells were lower in SVR than non-SVR. Proportions of CD4+ and CD8+ TEM and terminally differentiated effector memory (TEMRA) T cells declined on therapy in SVR, as did proportions of Fas+ CD8+ TEMRA T cells. Baseline frequencies of programmed death (PD)-1-expressing CD4+ TEM and T EMRA T-cells were higher in SVR. Therapy increased percentages of PD-1+ CD4+ central memory (TCM) T cells and PD-1+ CD8+ TEM and TEMRA T cells in SVR. We conclude that successful therapy depletes circulating antigen-specific CD4+ T cell responses. This paralleled decreases in proportions of effector memory T cells and higher percentages of CD4+ TCM T cells expressing PD-1. © 2010 British Society for Immunology.

Lee S.,Royal Perth Hospital | Lee S.,University of Western Australia | Varano J.,University of Western Australia | Flexman J.P.,Royal Perth Hospital | And 6 more authors.
Disease Markers | Year: 2010

The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy. © 2010 - IOS Press and the authors. All rights reserved.

Aghafar M.Z.K.A.,University of Western Australia | Witt C.,Clinical Immunology and Immunogenetics | Kamarulzaman A.,University of Malaya | Ismail R.,Universiti Sains Malaysia | And 5 more authors.
Tissue Antigens | Year: 2012

Polymorphisms in cell surface receptors of natural killer cells and their ligands on target cells can affect susceptibility to viral infections including human immunodeficiency virus (HIV)-1. We found that the carriage of the human leukocyte antigen (HLA)-G minus 14-bp polymorphism, LILRB1 single nucleotide polymorphism rs1061680, and activating and inhibitory killer immunoglobulin-like receptors (KIRs) were different when data were compared between Caucasian, African Americans and Asian populations. However, carriage was similar when HIV-1 patients were compared with control donors, with the exception of the African American cohort. © 2012 John Wiley & Sons A/S.

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