title: Discordant humoral and cellular immune responses toCytomegalovirus(CMV) in glioblastoma patients whose tumors are positive for CMV.
abstract: Background.Glioblastoma (GBM) is the most common malignant brain tumor in adults and is nearly always fatal. Emerging evidence suggests that humanCytomegalovirus(HCMV) is present in 90-100% of GBMs and that add-on antiviral treatment for HCMV show promise to improve survival.Methods.In a randomized, placebo-controlled trial of valganciclovir in 42 GBM patients, blood samples were collected for analyses of HCMV DNA, RNA, reactivity against HCMV peptides, IgG, and IgM at baseline and at 3, 12, and 24 weeks of treatment.Results.All 42 tumors were positive for HCMV protein. All patients examined had at least one blood sample positive for HCMV DNA, 63% were HCMV RNA positive, and 21% were IgM positive. However, 29% of GBM patients were IgG negative for HCMV. Five of these samples were positive in an enzyme-linked immunosorbent assay (ELISA) that used antigens derived from a clinical isolate. Blood T cells from 11 of 13 (85%) HCMV IgG-negative GBM patients reacted against HCMV peptides. Valganciclovir did not affect IgG titers, DNA, or RNA levels of theHCMV immediate early (HCMV IE)gene in blood.Conclusion.In GBM patients, HCMV activity is higher than in healthy controls and serology is a poor test to define previous or active HCMV infection in these patients.
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Departments of Neurosurgery; Karolinska University Hospital ; Stockholm, Sweden.
authors.forename: Inti
authors.initials: I
authors.lastname: Peredo
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Nina Wolmer
authors.initials: NW
authors.lastname: Solberg
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Chato
authors.initials: C
authors.lastname: Taher
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Mensur
authors.initials: M
authors.lastname: Dzabic
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Xinling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Skarman
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Olesja
authors.initials: O
authors.lastname: Fornara
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Tammik
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Koon
authors.initials: K
authors.lastname: Yaiw
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wilhelmi
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.affiliation: Neuropathology; Karolinska University Hospital ; Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Naucler
keywords: ELISA, enzyme-linked immunosorbent assay; FACS, flow cytometry analyses; FITC, fluorescein isothiocyanate; GBM, glioblastoma; HCMV IE, human Cytomegalovirus-immediate early; HCMV, human Cytomegalovirus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; PBMC, Peripheral blood mononuclear cells; PBS, Phosphate buffered saline; PCR, polymerase chain reaction; SEB, staphylococcal snterotoxin B; VIGAS study, Efficacy and Safety of Valcyte® as an Add-on Therapy in Patients with Malignant Glioblastoma and cytomegalovirus infection; Valcyte; cytomegalovirus; glioblastoma; peptides stimulation; serology; valganciclovir