Serum specific IgG response to toluene diisocyanate-tissue transglutaminase conjugate in toluene diisocyanate-induced occupational asthmatics.

Abstract

BACKGROUND: Tissue transglutaminase (tTG) is a post-translational modifying

enzyme located in airway epithelial cells. A potential contribution of serum

specific IgG (sIgG) to tTG in airway inflammation of toluene diisocyanate

(TDI)-induced occupational asthma (OA) has been suggested. OBJECTIVE: To prepare

a TDI-tTG conjugate and detect serum specific antibodies in sera of patients with

TDI-OA to understand this mechanism. METHODS: Ninety-nine patients with TDI-OA,

76 asymptomatic exposed controls, 208 patients with non-OA, and 74 unexposed

controls were enrolled for this study. The TDI-tTG conjugate was prepared and

confirmed by a native gel. Serum sIgG and/or sIgE antibodies to tTG, TDI-tTG, TDI

conjugated to human serum albumin, cytokeratin 19, and serum cytokine levels,

such as interleukin-8, transforming growth factor-beta1, and tissue inhibitor of

metalloproteinase-1, were measured by enzyme-linked immunosorbent assay. The

level of interleukin-8 produced from airway epithelial cells (A549) treated with

tTG was evaluated to investigate the inflammatory effect of tTG and TDI-tTG.

RESULTS: In the TDI-OA group, the prevalence of serum sIgG to TDI-tTG (17.2%) was

higher than that of sIgG to tTG (11.1%), which were significantly higher than

those of the 3 control groups (P < .05 for all groups). TDI-exposed subjects with

high levels of serum sIgG to TDI-tTG had a high prevalence of sIgG to cytokeratin

19 and higher serum levels of transforming growth factor-beta1 and tissue

inhibitor of metalloproteinase-1. The tTG and TDI-tTG dose-dependently increased

interleukin-8 production from A549 cells. CONCLUSION: These findings suggest that

TDI exposure in the workplace binds to tTG to form a conjugate that can induce

serum sIgG antibody production, airway inflammation, and airway remodeling in

patients with TDI-OA.