Le Duy Pham1, Mi-Ae Kim1, Moon Gyung Yoon1, Seung Ihm Lee1, Yoo Seob Shin1, Hae-Sim Park2. 1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. 2. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. Electronic address: hspark@ajou.ac.kr.
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-β1, 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-β1 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.
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 humanserum albumin, cytokeratin 19, and serum cytokine levels, such as interleukin-8, transforming growth factor-β1, 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-β1 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.