title: Lymphomagenesis-related gene expression in B cells from sustained virological responders with occult hepatitis C virus infection.
abstract: The expression of activation-induced cytidine deaminase, B-aggressive lymphoma, cyclin D1 and serine/threonine kinase 15 genes, among others, is increased in B cells from patients with chronic hepatitis C virus (HCV) infection. It is unknown whether the level of expression of these genes in B cells is increased in patients with hepatitis C who have achieved a sustained virological response (SVR) but who have persistent, detectable HCV RNA, so-called occult infection. Eighty-three patients who achieved and SVR, 27 with detectable HCV and 56 without detectable HCV RNA, 28 chronic hepatitis C patients and 32 healthy controls were studied. RNA was extracted from B cells, and gene expression levels were measured by RT-PCR. Patients with chronic HCV and those who achieved an SVR (with and without persistent low-level HCV RNA) showed a statistically significant higher expression compared to healthy controls, of activation-induced cytidine deaminase (P = 0.004, P < 0.001 and P = 0.002, respectively), B-aggressive lymphoma (P < 0.001, P = 0.001 and P = 0.006) and cyclin D1 (P = 0.026, P = 0.001; P = 0.038). For activation-induced cytidine deaminase patients with an SVR and 'occult infection' had a statistically significantly higher expression level than patients with and SVR without 'occult infection' (P = 0.014). The higher expression levels found for activation-induced cytidine deaminase, together with other genes indicates that these B lymphomagenesis-related genes are upregulated following HCV therapy and this is more marked when HCV can be detected in PBMCs.
authors.affiliation: Biomedicine Institute of Seville (IBIS), University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Roque Cuéllar
authors.affiliation: Department of Immunology, IBIS, University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: García-Lozano
authors.affiliation: Department of Immunology, IBIS, University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Sánchez
authors.affiliation: Statistics, Methodology and Research Evaluation Unit, Andalusian Public Foundation for Health Research Management in Seville (FISEVI), IBIS, University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Praena-Fernández
authors.affiliation: Department of Gastroenterology, University Hospital Virgen del Rocio, Seville, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martínez Sierra
authors.affiliation: Department of Immunology, IBIS, University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Núñez-Roldán
authors.affiliation: Biomedicine Institute of Seville (IBIS), University Hospital Virgen del Rocio, CSIC, University of Seville, Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Aguilar-Reina
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D063646:Carcinogenesis; D005260:Female; D020869:Gene Expression Profiling; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008223:Lymphoma / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D000072230:Sustained Virologic Response; D059467:Transcriptome; D055815:Young Adult
chemical_list: D012367:RNA, Viral
keywords: B lymphocytes; HCV persistence; Lymphomagenesis-related genes