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Biomarkers Predicting Isocyanate-Induced Asthma
Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers...
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Formato: | Texto |
Lenguaje: | English |
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The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005314/ https://www.ncbi.nlm.nih.gov/pubmed/21217921 http://dx.doi.org/10.4168/aair.2011.3.1.21 |
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author | Palikhe, Nami Shrestha Kim, Joo-Hee Park, Hae-Sim |
author_facet | Palikhe, Nami Shrestha Kim, Joo-Hee Park, Hae-Sim |
author_sort | Palikhe, Nami Shrestha |
collection | PubMed |
description | Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 µg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA. |
format | Text |
id | pubmed-3005314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease |
record_format | MEDLINE/PubMed |
spelling | pubmed-30053142011-01-08 Biomarkers Predicting Isocyanate-Induced Asthma Palikhe, Nami Shrestha Kim, Joo-Hee Park, Hae-Sim Allergy Asthma Immunol Res Review Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 µg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA. The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2011-01 2010-07-29 /pmc/articles/PMC3005314/ /pubmed/21217921 http://dx.doi.org/10.4168/aair.2011.3.1.21 Text en Copyright © 2011 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Palikhe, Nami Shrestha Kim, Joo-Hee Park, Hae-Sim Biomarkers Predicting Isocyanate-Induced Asthma |
title | Biomarkers Predicting Isocyanate-Induced Asthma |
title_full | Biomarkers Predicting Isocyanate-Induced Asthma |
title_fullStr | Biomarkers Predicting Isocyanate-Induced Asthma |
title_full_unstemmed | Biomarkers Predicting Isocyanate-Induced Asthma |
title_short | Biomarkers Predicting Isocyanate-Induced Asthma |
title_sort | biomarkers predicting isocyanate-induced asthma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005314/ https://www.ncbi.nlm.nih.gov/pubmed/21217921 http://dx.doi.org/10.4168/aair.2011.3.1.21 |
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