title: Endogenous antibody responsiveness to epidermal growth factor receptor is associated with immunoglobulin allotypes and overall survival of patients with glioblastoma.
abstract: BACKGROUND
  Immunoglobulin γ marker (GM) and κ marker (KM) allotypes, hereditary antigenic determinants of γ and κ chains, respectively, have been shown to be associated with immunity to a variety of self and nonself antigens, but their possible contribution to immunity to the tumor-associated antigens epidermal growth factor receptor (EGFR) and EGFR variant (v)III has not been evaluated. The aim of the present investigation was to determine whether the interindividual variation in endogenous antibody responsiveness to EGFR and EGFRvIII is associated with particular GM, KM, and Fcγ receptor (FcγR) genotypes and whether antibody levels were associated with the overall survival of patients with glioblastoma.
  
  
  METHODS
  A total of 126 Caucasian participants with glioblastoma were genotyped for several GM, KM, and FcγR alleles and characterized for IgG antibodies to EGFR and EGFRvIII antigens.
  
  
  RESULTS
  The anti-EGFR antibody levels associated with GM 3/3 homozygotes and GM 3/17 heterozygotes were similar (15.9 vs 16.4 arbitrary units [AU]/µL) and significantly lower than those associated with GM 17/17 homozygotes (19.6 AU/µL; nominal P = .007). Participants homozygous for the GM 21 allele also had significantly higher levels of anti-EGFR antibodies than GM 5/5 homozygotes and GM 5/21 heterozygotes (20.1 vs 16.0 and 16.3 AU/µL; nominal P = .005). Similar associations were found with immune responsiveness to EGFRvIII. Higher anti-EGFR and anti-EGFRvIII antibody levels were associated with enhanced overall survival (16 vs 11 mo, nominal P = .038 and 20 vs 11 mo, nominal P = .004, respectively).
  
  
  CONCLUSIONS
  GM allotypes contribute to humoral immunity to EGFR in glioblastoma.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Janardan P
authors.initials: JP
authors.lastname: Pandey
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Emily
authors.initials: E
authors.lastname: Kistner-Griffin
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Faisal F
authors.initials: FF
authors.lastname: Radwan
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Navtej
authors.initials: N
authors.lastname: Kaur
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Aryan M
authors.initials: AM
authors.lastname: Namboodiri
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Laurel
authors.initials: L
authors.lastname: Black
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Butler
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Tania
authors.initials: T
authors.lastname: Carreon
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina (J.P.P., F.F.R., N.K., A.M.N., L.B.); Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina (E.K-G.); Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio (M.A.B., T.C., A.M.R.).
authors.forename: Avima M
authors.initials: AM
authors.lastname: Ruder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics* / Q000276:immunology*; D007131:Immunoglobulin Km Allotypes / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics; D013534:Survival; D055815:Young Adult
chemical_list: D007129:Immunoglobulin Gm Allotypes; D007131:Immunoglobulin Km Allotypes; D017452:Receptors, IgG; D066246:ErbB Receptors
keywords: EGFR; EGFRvIII; GM allotypes; antibody; glioblastoma