Expression Profiling of Peripheral-Blood Mononuclear Cells from Patients with Chronic Hepatitis C Undergoing Interferon Therapy

Tateno, Makoto; Honda, Masao; Kawamura, Takashi; Honda, Hiroyuki; Kaneko, Shuichi
January 2007
Journal of Infectious Diseases;1/15/2007, Vol. 195 Issue 2, p255
Academic Journal
Background. Interferon (IFN) is now the standard treatment for chronic hepatitis C (CH-C); however, treatment efficacy is unpredictable before IFN therapy is started. Methods. We investigated the gene-expression profiles of peripheral-blood mononuclear cells (PBMCs) from patients with CH-C showing different responses to IFN. Gene-expression profiles of PBMCs were analyzed in 21 patients with CH-C treated with IFN alone or in combination with ribavirin as well as in 6 healthy volunteers. Serial changes in the gene-expression profiles of PBMCs from individual patients were evaluated before treatment, 2 weeks after the start of IFN therapy, and 6 months after the completion of IFN therapy. Results. Interestingly, the gene-expression profiles of PBMCs from patients with CH-C and healthy volunteers differed substantially; early T cell-activation antigen CD69 was significantly up-regulated in patients with CH-C, but immune-related molecules such as chemokine (C-C motif) receptor 2 and interleukin 7 receptor were significantly down-regulated. Selected combinations of expressed genes obtained before treatment and during IFN therapy by use of a fuzzy neural network combined with the SWEEP operator method predicted the outcome of IFN therapy with peak accuracies of 91.0% and 90.2%, respectively. Conclusions. These findings suggest that the gene-expression profiles of PBMCs from patients with CH-C may be useful biomarkers for IFN therapy.


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