Increased levels of IgG to cytokeratin 19 in sera of patients with toluene diisocyanate-induced asthma.
BACKGROUND
Inhaled isocyanate binds with cytokeratin (CK) of the epithelial cells, which could induce immune responses.


OBJECTIVE
To elucidate the possible existence of an isocyanate-induced, asthma-associated autoantigen from the bronchial epithelial cells, which may be associated with toluene diisocyanate (TDI)-induced asthma development.


METHODS
We cultured bronchial epithelial cells with incubation of TDI-human serum albumin (HSA) conjugate. Gene expression profiles of cultured epithelial cells were analyzed using a microarray technique. CK19 protein expression within the epithelial cells was confirmed by IgG immunoblot using monoclonal antibody to CK19. Serum IgG to CK19 and specific IgG and IgE antibodies to TDI-HSA conjugate were detected by enzyme-linked immunosorbent assay in 68 TDI asthma patients (group 1) and compared with 40 allergic asthma patients (group 2) and 80 unexposed healthy controls (group 3).


RESULTS
After TDI exposure, increased expression of CK19 and CK14 genes from the culture bronchial epithelial cells was noted using microarray analysis. IgG immunoblot analysis confirmed increased expression of CK19 after the TDI exposure. The levels of serum IgG to CK19 were significantly higher in the TDI asthma group than in groups 2 and 3 (P=.008). The prevalence of IgG to CK19 was significantly higher in group 1 (38.2%) than group 2 (22.5%) or group 3 (1.3%) (P=.008). Significant associations were noted between IgG to CK19 and specific IgG to TDI-HSA conjugate and transglutaminase (P=.02) but not with specific IgE to TDI-HSA conjugate.


CONCLUSIONS
We suggest that TDI exposure can augment CK19 expression from the bronchial epithelial cell, which may involve immune responses as an autoantigen to induce airway inflammation in TDI-induced asthma.
Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
Jung-Hee
JH
Choi
Dong-ho
DH
Nahm
Seung-Hyun
SH
Kim
Young-Suk
YS
Kim
Chang-Hee
CH
Suh
Hae-Sim
HS
Park
Sung-Wan
SW
Ahn
D000328:Adult; D000485:Allergens / Q000009:adverse effects; D000918:Antibody Specificity; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000187:drug effects / Q000276:immunology*; D001980:Bronchi / Q000166:cytology; D001985:Bronchial Provocation Tests; D002461:Cell Line, Transformed / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007633:Keratins / Q000187:drug effects / Q000276:immunology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D012709:Serum Albumin / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects* / Q000493:pharmacokinetics
D000485:Allergens; D001323:Autoantibodies; D001324:Autoantigens; D018796:Immunoconjugates; D007074:Immunoglobulin G; D012333:RNA, Messenger; D012709:Serum Albumin; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; D007633:Keratins