Antibodies to varicella-zoster virus and three other herpesviruses and survival in adults with glioma

Abstract

Background Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however the relationship of VZV with survival in adults with glioma has not been investigated. In this study, we analyzed survival of adults with glioma in relation to their antibody measurements to 4 common herpes viral infections, including VZV, measured post-diagnosis. Materials and Methods We analyzed IgG antibody measurements to VZV, cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and Epstein-Barr virus (EBV) collected from 1378 adults with glioma diagnosed between 1991 and 2010. Blood was obtained a median of 3 months after surgery. Associations of patient IgG levels with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw, and tumor grade. Models were stratified by recruitment series and meta-analyzed to account for time-dependent treatment effects. Results VZV antibody seropositivity was associated with improved survival outcomes in adults with glioma (Hazard ratio, HR=0.70, 95% Confidence Interval 0.54-0.90, p=0.006). Amongst cases who were seropositive for VZV antibodies, survival was significantly improved for those above the 25th percentile of continuous reactivity measurements versus those below (HR=0.76, 0.66-0.88, p=0.0003). Antibody seropositivity to EBV was separately associated with improved survival (HR=0.71, 0.53-0.96, p=0.028). Antibody positivity to two other common viruses (CMV, HSV) was not associated with altered survival. Conclusions Low levels of VZV or EBV antibodies are associated with poorer survival outcomes for adults with glioma. Differential immune response rather than viral exposure may explain these findings.

Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival

“…History of infection with varicella zoster virus (VZV), a neurotropic α-herpesvirus that causes chickenpox and shingles 6,7 , and the presence of IgG antibodies to VZV 7 have been inversely associated with glioma risk. This has recently extended to prognosis, where stronger VZV reactivity was associated with improved survival 8 . History of allergies or other atopic conditions (hay fever, eczema, and asthma) [9][10][11][12] and increased IgE levels 13,14 have been associated with a decreased risk of glioma in multiple observational studies.…”

Association of immunoglobulin E levels with glioma risk and survival

“…GBM has a clear sex bias, where males are more likely to develop glioma and have poorer outcomes than females 4 . In the last two decades, epidemiologic studies have highlighted a putative role of immune-related factors, including viral infections 5,6 , allergic conditions 7 and autoimmune disorders 8 , in gliomagenesis.…”