Unknown,Transcriptomics,Genomics,Proteomics

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CD4+ T cell gene expression in virologically suppressed HIV-infected patients during Maraviroc intensification therapy.

ABSTRACT: Analysis of CD4+ T cell gene expression changes after 4 and 24 weeks of Maraviroc administration relative to baseline in 25 immunodiscordant patients with viral suppression. Maraviroc elicited very modest changes in CD4+ T cell transcriptome. The goal of this study was to identify genes with a potential role in Maraviroc-induced CD4+ T cell recovery in immunodiscordant patients. The study measured gene expression in CD4+ T cells isolated from the whole blood of HIV-infected patients before and at two time points after addition of Maraviroc to the baseline antiretroviral therapy. Thirty two patients were recruited from 3 sites, University of California, San Diego (UCSD), University of California, Los Angeles (UCLA) and University of Southern California (USC), and peripheral blood samples were obtained at 3 visits, week 0 (baseline), week 4 and week 24 after initiation of Maraviroc therapy. Because of poor RNA quality and outliers on the microarrays, 7 patients were excluded from the study. Non-outlier week 0 and week 24 arrays from one of the patients (Patient ID 01-005) were used for array data normalization and processing, but were not included in the time course analysis since the week 4 sample was not available.

ORGANISM(S): Homo sapiens

SUBMITTER: Nadejda Beliakova-Bethell

PROVIDER: E-GEOD-56804 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Coeliac disease is a small intestinal disorder caused by an abarrent immune response towards dietary gluten due to activation of pro-inflammatory gluten specific CD4+ T cells. Histological evaluation and classification of gluten induced musosal changes is part of the diagnostic work up. of adults. The kinetics of mucosal recovery following commencesment of a gluten free diet (disease remission) and the degree of mucosal changes induced by gluten reintroduction (gluten challenge) varies between patients. Also, patients classified with similar clinical and histological disease remission, can develop different degree of mucosal damage following the same gluten challenge regime. This variation poses a challenge for the interpretation of gluten induced mucosal changes both in a diagnostic and clinical trial settings. In this study, we have analysed material from small intestinal biopsies collected from 19 treated coeliac disease patients before and after completion of a 14-day oral gluten challenge. These patients are part of a previoslpreviouslyu described study where all patients were in clinical and mucosal remission at baseline but only some patients developed histological changes in the mucosa in response to gluten. We have performed shotgun LC-MSMS analysis and label-free quantification of total gut tissue and from laser capture microdissected epithelial cell layer samples. We found that differences in tissue proteome expression could separate patients as responders and non-responders to the gluten challenge. Patients whoich responded strongly to gluten , had signs of gut inflammation already at baseline, supported by presence of low-level blood inflammatory parameters and a slight increase in numbers of gluten-specific CD4+ T cells at baseline. Our proteomics analysis demonstrated baseline differences in gut tissue state between patients that were not evident from routine clinical and histological evaluation. These baseline differences likely explains why some patients respond more strongly to gluten challenge than others.

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CD4+ T cell gene expression in virologically suppressed HIV-infected patients during Maraviroc intensification therapy.

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