Association of immunoglobulin E levels with glioma risk and survival

Abstract

Background: Previous epidemiological studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.

Methods: We conducted a case-control study using participants from the University of California San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory, and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free control individuals (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided.

Results: Elevated total IgE was associated with reduced risk of IDH wild-type glioma (risk ratio [RR] = 0.78, 95% CI = 0.71 to 0.86) and IDH-mutant glioma (RR = 0.73, 95% CI = 0.63 to 0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH wild-type glioma (RR = 0.79, 95% CI = 0.67 to 0.93). The reduction in mortality risk was statistically significant in female individuals only (RR = 0.75, 95% CI = 0.57 to 0.98), with an improvement in median survival of 6.9 months (P < .001).

Conclusion: Elevated serum IgE was associated with improved prognosis for IDH wild-type glioma, with a more pronounced protective effect in female than male individuals, which has implications for the future study of IgE-based immunotherapies for glioma.

Figure 1.

Associations between immunoglobulin E (IgE) levels and survival, stratified by sex and molecular subtype. Risk ratios (RR) and corresponding 95% CIs were estimated using inverse probability of treatment weighted Cox regression models. Propensity models included age, sex (included in combined analysis only), self-reported race and ethnicity, and chemotherapy use. Weighted Cox models were also adjusted for dexamethasone use, surgery type (resection or biopsy only), 1p19q co-deletion status, TERT variation, tumor grade, and Adult Glioma Study recruitment series. The RR estimate for food IgE and IDH-mutant glioma (combined and female only) are not shown because of an insufficient number of individuals with positive food IgE.

Figure 2.

Kaplan-Meier curves for adult glioma cases with serum immunoglobulin E (IgE) concentrations. The percentage of survival distributions for adults with glioma, stratified by sex and categorical serum IgE concentration for (A) IDH wild-type glioma and total IgE and (B) IDH wild-type glioma and respiratory IgE. +IgE = above-normal total IgE or positive respiratory IgE. –IgE = normal total IgE or negative respiratory IgE. P values are shown for the sex-stratified Kaplan-Meier curves.

Figure 3.

Population-attributable fractions for IDH wild-type survival, stratified by sex and follow-up time. Population -attributable fraction estimates for age at diagnosis (<58 years vs ≥58 years), surgery (resection vs biopsy), chemotherapy use (yes vs no), and respiratory immunoglobulin E (IgE) (positive vs negative) were derived from Cox proportional hazards regression models adjusted for sex (combined only), self-reported race and ethnicity, radiation use, 1p19q co-deletion status, TERT variation status, and strata for tumor grade. Estimates are reported for 6 months and 12 months of follow-up time. Estimates that do not achieve P < .05 are indicated by a striped pattern.