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Endogenous antibody responsiveness to epidermal growth factor receptor is associated with immunoglobulin allotypes and overall survival of patients with glioblastoma.

Authors
Pandey-JP; Kistner-Griffin-E; Radwan-FF; Kaur-N; Namboodiri-AM; Black-L; Butler-MA; Carreon-T; Ruder-AM
Source
Neuro-Oncology 2015 May; 17(5):678-684
NIOSHTIC No.
20045270
Abstract
Background. Immunoglobulin gamma marker (GM) and kappa marker (KM) allotypes, hereditary antigenic determinants of gamma and kappa 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 Fcgamma receptor (FcgammaR) 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 FcgammaR 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]/microL) and significantly lower than those associated with GM 17/17 homozygotes (19.6 AU/microL; 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/microL; 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.
Keywords
Immune-reaction; Immune-system; Immunoglobulins; Antigens; Cancer; Oncogenic-agents; Biomarkers; Tumors; Antibody-response; Growth-factors; Brain-tumors; Genetic-factors; Survival-rate; Humans; Genes
Contact
Janardan P. Pandey, PhD, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425-2230
CODEN
NEURJR
Publication Date
20150501
Document Type
Journal Article
Email Address
pandeyj@musc.edu
Fiscal Year
2015
NTIS Accession No.
NTIS Price
Identifying No.
M102014
Issue of Publication
5
ISSN
1522-8517
NIOSH Division
DART; DSHEFS
Source Name
Neuro-Oncology
State
SC; OH
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