Yonsei Med J.  2006 Dec;47(6):773-781. 10.3349/ymj.2006.47.6.773.

Cytokeratin Autoantibodies: Useful Serologic Markers for Toluene Diisocyanate-Induced Asthma

• Ye YM
• Nahm DH
• Kim CW
• Kim HR
• Hong CS
• Park CS
• Suh CH
• Park HS

• KMID: 1777164
• DOI: http://doi.org/10.3349/ymj.2006.47.6.773

Abstract

To evaluate the clinical significance of autoantibodies to three major epithelial cytokeratins (CK) -- CK8, CK18, and CK19 -- we compared 66 patients with toluene diisocyanate (TDI)-induced asthma (group I) with three control groups: 169 asymptomatic exposed subjects (group II), 64 patients with allergic asthma (group III), and 123 unexposed healthy subjects (group IV). Serum IgG, specific for human recombinant CKs, were measured by ELISA (enzyme linked immunosorbent assay), and ELISA inhibition tests were performed. The existence of these antibodies was confirmed by IgG immunoblot analysis. Anti-TDI-HSA (human serum albumin) IgE and IgG antibodies were measured by ELISA in the same set of the patients. The prevalence of CK8, CK18, and CK19 auotantibodies in group I was significantly higher than in the other three groups. Results of the ELISA inhibition test showed significant inhibition with the addition of three CKs in a dose-dependent manner. No significant association was found between CK autoantibodies and the prevalence of anti- TDI-HSA IgG and IgE antibodies. These results suggest that autoantibodies to CK18 and CK19 can be used as serologic markers for identifying patients with TDI-induced asthma among exposed workers.

Keyword

Isocyanate; asthma; cytokeratin; diagnosis

MeSH Terms

Toluene 2,4-Diisocyanate/*toxicity
Sensitivity and Specificity
Occupational Diseases/chemically induced/*diagnosis
Middle Aged
Male
Keratins/*immunology
Keratin-8/immunology
Keratin-19/immunology
Keratin-18/immunology
Immunoblotting
Humans
Female
Enzyme-Linked Immunosorbent Assay
Biological Markers/blood
Autoantibodies/*blood
Asthma/chemically induced/*diagnosis
Adult

Figure

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  Fig. 1 Detection of CK8 (A), CK18 (B), and CK19 (C) autoantibodies by ELISA in serum samples from the four subject groups. Group I, patients with TDI-induced asthma; group II, asymptomatic exposed workers; group III, patients with allergic asthma; and group IV, healthy control subjects. Horizontal bars indicate positive cutoff values. The ANOVA and post hoc Scheffe test were applied to compare the level of specific IgG to CKs 8, 18, and 19 among the four study groups.

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  Fig. 2 ELISA inhibition test results for three cytokeratins - CK8 (A), CK18 (B), and CK19 (C) - with serial additions of each cytokeratin (●, CK8; ■, CK18; ▲, CK19).

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  Fig. 3 Immunoblot analysis of recombinant CK8, CK18, and CK19, using serum samples from patients with TDI-induced asthma (TDI), unexposed healthy control subjects (NC), buffer-only samples or (B) monoclonal antibodies (M) to the three cytokeratins.

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