title: Whole CMV proteome pattern recognition analysis after HSCT identifies unique epitope targets associated with the CMV status.
abstract: Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/- for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the 'exclusive recognition analysis (ERA)' to identify unique CMV epitope responses for each patient group. The 'exclusive recognition analysis' of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D-/R-). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution.
authors.affiliation: Department of Medicine Huddinge, Karolinska Institutet; Dept. of Hematology, Karolinska University Hospital, Stockholm, Sweden; CAST (Center for allogeneic stem cell transplantation), Karolinska Hospital.
authors.forename: Lena
authors.initials: L
authors.lastname: Pérez-Bercoff
authors.affiliation: CAST (Center for allogeneic stem cell transplantation), Karolinska Hospital.
authors.forename: Davide
authors.initials: D
authors.lastname: Valentini
authors.affiliation: Microbiology, Tumor and Cell Biology (MTC), Stockholm, Sweden.
authors.forename: Simani
authors.initials: S
authors.lastname: Gaseitsiwe
authors.affiliation: The Swedish Institute for Infectious Disease Control (SMI), Stockholm, Sweden.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Mahdavifar
authors.affiliation: Department of Enzymology, Institute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.affiliation: Division of Therapeutic Immunology (TIM), LabMed Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Poiret
authors.affiliation: Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Pérez-Bercoff
authors.affiliation: Department of Medicine Huddinge, Karolinska Institutet; Dept. of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.affiliation: CAST (Center for allogeneic stem cell transplantation), Karolinska Hospital; Division of Therapeutic Immunology (TIM), LabMed Karolinska Institutet, Stockholm, Sweden.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology; D040081:Protein Array Analysis; D020543:Proteome; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D020543:Proteome; D014764:Viral Proteins
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