title: Whole Transcriptome Profiling Identifies CD93 and Other Plasma Cell Survival Factor Genes Associated with Measles-Specific Antibody Response after Vaccination.
abstract: BACKGROUND
  There are insufficient system-wide transcriptomic (or other) data that help explain the observed inter-individual variability in antibody titers after measles vaccination in otherwise healthy individuals.
  
  
  METHODS
  We performed a transcriptome(mRNA-Seq)-profiling study after in vitro viral stimulation of PBMCs from 30 measles vaccine recipients, selected from a cohort of 764 schoolchildren, based on the highest and lowest antibody titers. We used regression and network biology modeling to define markers associated with neutralizing antibody response.
  
  
  RESULTS
  We identified 39 differentially expressed genes that demonstrate significant differences between the high and low antibody responder groups (p-value≤0.0002, q-value≤0.092), including the top gene CD93 (p<1.0E-13, q<1.0E-09), encoding a receptor required for antigen-driven B-cell differentiation, maintenance of immunoglobulin production and preservation of plasma cells in the bone marrow. Network biology modeling highlighted plasma cell survival (CD93, IL6, CXCL12), chemokine/cytokine activity and cell-cell communication/adhesion/migration as biological processes associated with the observed differential response in the two responder groups.
  
  
  CONCLUSIONS
  We identified genes and pathways that explain in part, and are associated with, neutralizing antibody titers after measles vaccination. This new knowledge could assist in the identification of biomarkers and predictive signatures of protective immunity that may be useful in the design of new vaccine candidates and in clinical studies.
authors.affiliation: Mayo Clinic Vaccine Research Group-Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.affiliation: Division of Biomedical Statistics and Informatics- Department of Health Science Research, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Zimmermann
authors.affiliation: Mayo Clinic Vaccine Research Group-Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.affiliation: Division of Biomedical Statistics and Informatics- Department of Health Science Research, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Grill
authors.affiliation: Division of Biomedical Statistics and Informatics- Department of Health Science Research, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Ann L
authors.initials: AL
authors.lastname: Oberg
authors.affiliation: Mayo Clinic Vaccine Research Group-Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.affiliation: Mayo Clinic Vaccine Research Group-Department of Medicine, Mayo Clinic and Foundation, Rochester, MN, United States of America.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D002470:Cell Survival / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008459:Measles virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D011951:Receptors, Complement / Q000235:genetics*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor