Expression profiling of peripheral-blood mononuclear cells from patients with chronic hepatitis C undergoing interferon therapy.
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.
Tateno
Makoto
M
Department of Cancer Gene Regulation, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.
Honda
Masao
M
Kawamura
Takashi
T
Honda
Hiroyuki
H
Kaneko
Shuichi
S
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D037181:Lectins, C-Type; D011506:Proteins; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D012254:Ribavirin; D000099192:CD69 Antigens