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Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

ABSTRACT: Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous CD8+ T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation - pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with CD4+ T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy.

SUBMITTER: Lee JC

PROVIDER: S-EPMC3196314 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

Lee James C JC Lyons Paul A PA McKinney Eoin F EF Sowerby John M JM Carr Edward J EJ Bredin Francesca F Rickman Hannah M HM Rickman Hannah M HM Ratlamwala Huzefa H Hatton Alexander A Rayner Tim F TF Parkes Miles M Smith Kenneth G C KG

The Journal of clinical investigation 20110926 10

Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of u ...[more]

PMID: 21946256

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Project description:To formulate therapy goals, we aimed to define the relationship between fecal calprotectin and health-related quality of life in inflammatory bowel diseases (IBDs). This retrospective single-center cross-sectional study included ambulatory IBD patients who had completed standardized questionnaires comprising items of health-related quality of life (Short Inflammatory Bowel Disease Questionnaire) and clinical disease activity scores, and who had provided stool samples for calprotectin determination within 30 days of questionnaire completion. Correlation analyses were performed between the indicated parameters. Post hoc analysis was conducted, taking into account only data from patients with fecal calprotectin concentrations measured within 3 days of questionnaire completion. One hundred ninety-seven patients with Crohn disease and 111 patients with ulcerative colitis were enrolled in the study. Lower fecal calprotectin concentrations were associated with better health-related quality of life. The correlations were weak, but stronger if only fecal calprotectin concentrations measured within 3 days of questionnaire completion were included (results for 3 days; Crohn disease: n?=?86, rS?=?-0.419, P?<?0.001; ulcerative colitis: n?=?43, rS?=?-0.432, P?=?0.004). In Crohn disease, a significant correlation between fecal calprotectin concentration and health-related quality of life was found in patients with colonic involvement (n?=?59, rS?=?-0.470, P?<?0.001), but not in patients with purely ileal disease (n?=?27, rS?=?-0.268, P?=?0.18). Correlations between fecal calprotectin concentrations and clinical disease activity were also only weak to moderate. Owing to its moderate correlation with fecal calprotectin concentrations in IBD patients with colonic involvement, health-related quality of life should be used in combination with other markers for IBD management. This is even more important in isolated ileal Crohn disease, where no significant correlation between fecal calprotectin concentration and health-related quality of life was found. Especially for use in research studies, care should be taken to keep the time between clinical evaluation of IBD patients and the determination of fecal calprotectin concentrations as short as possible.

Dataset Information

Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

Publications

Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

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