title: 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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Le Duy
authors.initials: le D
authors.lastname: Pham
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Moon Gyung
authors.initials: MG
authors.lastname: Yoon
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Seung Ihm
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. Electronic address: hspark@ajou.ac.kr.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology; D059366:Asthma, Occupational / Q000097:blood* / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D053539:Keratin-19 / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000276:immunology; D011503:Transglutaminases / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D016209:Interleukin-8; D053539:Keratin-19; D012709:Serum Albumin; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; D011503:Transglutaminases