Circulating Levels of the Innate and Humoral Immune Regulators CD14 and CD23 Are Associated with Adult Glioma

Abstract

Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1079 glioma patients post diagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 (highest vs. lowest quartile OR = 3.94 (95% CI: 2.98-5.21) and low sCD23 (lowest vs. highest quartile OR=2.5 (95% CI: 1.89-3.23)). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. While temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, and in particular immunoregulatory proteins, in gliomagenesis.

Risk factors for gliomas. An extensive review

“…sCD23, a soluble marker, part of the humoral immune system, that enhances inflammatory response, is lower in GBM patients than controls (107). sDC14 that inhibits inflammatory response, is higher in GBM group vs. controls (107). Two subtypes of Interleukin (IL)-4 and IL-3 were also associated with GBM, and OR for GBM were opposite of the ones for asthma (108).…”

“…It seems that function of immune cells is altered in patients with GBM, in the sense that instead of preventing tumor appearance, immunity mechanisms support it (106). sCD23, a soluble marker, part of the humoral immune system, that enhances inflammatory response, is lower in GBM patients than controls (107). sDC14 that inhibits inflammatory response, is higher in GBM group vs. controls (107).…”

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study

“…These associations have been examined using single- [i.e., (11)], multi-site [i.e., (12–14)], and nested case-control studies [i.e., (15, 16)], prospective cohort studies [i.e., (3)], and meta-analyses [i.e., (1, 2, 7)]. Additionally, the observed inverse association between allergies and glioma has remained consistent across studies with different exposure assessment strategies, such as self-reported allergy status (3), self-reported physician-diagnosed allergies (12, 13, 17–19), number of allergy types (12, 17), and allergy-related biomarkers, such as Immunoglobulin E [overall (4, 11, 16, 20), pre-diagnostic (16, 21), and/or allergen-specific (11, 15, 16)], soluble CD23 levels (22), and polymorphisms in allergy-related genes (23–26). As the literature approaches a consensus on the relationship between allergies and glioma risk, our large consortium, the Glioma International Case-Control Study (GICC), provides an unprecedented opportunity to not only confirm the previously reported associations between atopy and glioma in the largest available study population, but also to hone in on the specific role of respiratory allergies.…”

A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma

“…However, no study has examined the influence of the miR-146a variant in glioma. Based on a growing body of evidence regarding the functional role of miR-146a in tumorigenesis and other physiological processes (i.e., innate immune and inflammatory responses) linked to gliomagenesis [21–23], we hypothesized that miR-146a rs2910164 may be associated with glioma risk and/or prognosis. Herein we report results from our evaluation of rs2910164 in a large series of glioma cases and controls enrolled in the case–control Study of Glioma in the Southeast ( GliomaSE ), a multi-center, clinic-based case–control study conducted at medical centers in the Southeastern United States (US).…”