title: Immune reconstitution after allogeneic hematopoietic stem cell transplantation is associated with selective control of JC virus reactivation.
abstract: JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. The mechanism of JCV reactivation and immunity in a transplanted immune system remains unclear. We prospectively studied 30 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and collected blood and urine samples before HSCT and 3, 6, and 12 to 18 months after HSCT. Before HSCT, JCV DNA was detected in 7 of 30 urine, 5 of 30 peripheral blood mononuclear cells (PBMC) and 6 of 30 plasma samples. Although JC viruria remained stable after HSCT with detection in 5 of 21 samples, viremia was detected in only 1 of 22 plasma and none of 22 PBMC samples 12 to 18 months after HSCT. Prevalence of anti-JCV IgG was 83% before HSCT and decreased to 72% at 12 to 18 months. Anti-JCV IgM was rarely detected. JCV-specific CD4(+) and CD8(+) T cell responses increased 12 to 18 months after HSCT. Although JC viruria correlated directly with detection of anti-JCV IgG, the cellular immune response to JCV measured by ELISpot was inversely correlated with anti-JCV IgG response. The diagnosis of acute myelogenous leukemia and age group were 2 independent patient factors associated with significantly reduced cellular immune responses to JCV. This prospective study in HSCT patients provides a model of interactions between the host immune response and viral activation in multiple compartments during the recovery of the immune system.
authors.affiliation: Center of Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: ctan@bidmc.harvard.edu.
authors.forename: Chen Sabrina
authors.initials: CS
authors.lastname: Tan
authors.affiliation: Center of Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Broge
authors.affiliation: Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Long
authors.initials: L
authors.lastname: Ngo
authors.affiliation: Center of Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gheuens
authors.affiliation: Department of Pediatrics, Johns Hopkins Medical Center, Baltimore, Maryland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Viscidi
authors.affiliation: Center of Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Bord
authors.affiliation: Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Jacalyn
authors.initials: J
authors.lastname: Rosenblatt
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; The Transplant Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.affiliation: Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Avigan
authors.affiliation: Center of Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Division of NeuroVirology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007577:JC Virus / Q000276:immunology / Q000502:physiology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology / Q000821:virology*; D008297:Male; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000276:immunology
keywords: HSCT; Immunocompromised host; JC virus