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 1,079 glioma patients postdiagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 [highest versus lowest quartile odds ratio (OR), 3.94; 95% confidence interval (95% CI), 2.98-5.21] and low sCD23 (lowest versus 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. Whereas 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, in particular immunoregulatory proteins, in gliomagenesis.

Fig 1

Analysis of joint odds ratio (OR) of sCD23 and sCD14 in glioblastoma (GBM) patients taking or not taking dexamethasone. The patients were stratified into four groups by ln sCD14 and ln s CD23 values (ln sCD14 <2.23 or >2.23, ln sCD23 <0.46 or >0.46). A. In GBM patients who were not taking dexamethasone at the time of blood draw the OR in the group with high sCD14 and low sCD23 was more than 6.8-fold higher than the group with the low sCD14 and high sCD23 values. B. In GBM patients who were taking dexamethosone the OR in the high sCD14 and low sCD23 was more than 14-fold higher than those with the low sCD14 and high sCD23 values.