Genetic markers of immunoglobulin G and immunity to cytomegalovirus in patients with breast cancer

Cell Immunol. 2017 Feb:312:67-70. doi: 10.1016/j.cellimm.2016.11.003. Epub 2016 Nov 2.

Abstract

Human cytomegalovirus (CMV), a ubiquitous herpesvirus, has been implicated in the etiology of breast cancer. It is clear that not all people exposed to CMV are equally likely to develop this malignancy, implying the presence of host genetic factors that might modulate the cancer-spurring properties of the virus. CMV has evolved sophisticated strategies for evading host immunosurveillance. One strategy involves encoding decoy Fcγ receptors (FcγR) that thwart the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity. In this investigation, using an enzyme-linked immunosorbent assay (ELISA), we aimed to determine whether the decoy FcγR encoded by the CMV gene RL13 binds differentially to anti-CMV antibodies expressing different immunoglobulin GM (γ marker) allotypes, genetic markers of immunoglobulin G (IgG). Results of our ELISA binding studies showed that the absorbance values for the binding of the viral FcγR to the GM 17-expressing IgG antibodies were significantly higher than for the GM 3-expressing antibodies (0.60 vs. 0.36; p=0.0019). These findings provide mechanistic insights into the modulating role played by the genetic variants of IgG in the generation of immunity to CMV in patients with breast cancer.

Keywords: Cytomegalovirus; Decoy Fcγ receptor; GM allotypes; Immunoevasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / metabolism
  • Antibody Affinity
  • Black or African American
  • Breast Neoplasms / immunology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immune Evasion
  • Immunoglobulin G / metabolism
  • Immunoglobulin Gm Allotypes / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Protein Binding
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin Gm Allotypes
  • Receptors, IgG
  • Viral Proteins