Circulating Soluble CD27 and CD30 in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

Abstract

Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. In this cross-sectional study, we investigated changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among workers of a cohort occupationally exposed to TCDD. Eighty-five workers who had been exposed to TCDD more than 30 years before blood collection were included in the current investigation. Plasma level of the markers was measured by ELISA. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high-resolution mass spectrometry. TCDD blood levels at time of last exposure were estimated using a one-compartment first order kinetic model. Exposure-response analyses showed no significant association between blood levels of sCD27, and sCD30 and current and estimated TCDD levels at time of last exposure. IL1RA showed a borderline significant decrease with increasing plasma TCDD levels (P ¼ 0.07), which reached formal statistical significance when excluding subjects with chronic diseases. In conclusion, no clear dose-response relationship was observed between the measured markers and TCDD level. However, there was a suggestion that markers in particular IL1RA tended to decrease with increasing TCDD levels. This observation is consistent with our earlier observation on decreasing cytokine levels, suggesting immunosuppression, with increasing exposures. These findings possibly provide new insights in the etiology of NHL and the mechanisms through which TCDD can increase lymphoma risk. Cancer Epidemiol Biomarkers Prev; 22(12);

Soluble B‐cell activation marker of sCD27 and sCD30 and future risk of B‐cell lymphomas: A nested case‐control study and meta‐analyses

“…Elevated levels of soluble CD27, cleaved from CD27‐positive cells, have been observed in many infectious and autoimmune diseases and have been proposed as a marker of immune activation . Recently, two studies have shown that exposure to environmental exposures suspected to be lymphomagens ( i.e ., trichloroethylene and 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin) pertubated plasma levels of sCD27 and sCD30 . This may indicate that lymphomagens exert their effect by dysregulation of the immune system as represented by changes in the B‐cell activation markers.…”

“…12 Recently, two studies have shown that exposure to environmental exposures suspected to be lymphomagens (i.e., trichloroethylene and 2,3,7,8-tetrachlorodibenzo-p-dioxin) pertubated plasma levels of sCD27 and sCD30. 30,31 This may indicate that lymphomagens exert their effect by dysregulation of the immune system as represented by changes in the B-cell activation markers.…”

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

“…Saberi Hosnijeh et al. (, , ) investigated immune parameters in occupational cohorts of workers exposed from 1953 to 1969, or from 1955 to 1986, with accidental high exposure in 1963. The studies were based on a small numbers of subjects on the same or overlapping cohorts.…”

Dioxin(-like)-Related Biological Effects through Integrated Chemical-wide and Metabolome-wide Analyses

“…To explore the potential mechanisms underlying dioxin­(-like) exposure toxicity, we used a network-based integration approach to evaluate the relationship between the metabolic pathways associated with dioxin­(-like) exposures and immune phenotypic end points. Immune markers, including cytokines and growth factors ( n = 21), hematologic parameters (i.e., cell counts) ( n = 23), humoral immunity markers [immunoglobulins (Ig) and complement factors (C)] ( n = 7), and lymphoma makers ( n = 3), were previously measured for factory A workers − (Table S3).…”