Serum Cytokine Levels as Serologic Markers of Toluene Diisocyanate-induced Occupational Asthma

Kim, J.; Choi, Gil Soon; Jin, Hyun Jung; Lee, J.; Sung, Jun-Mo; Ye, Y.; Nahm, Dong Ho; Park, H.

doi:10.1016/j.jaci.2009.12.323

Cited by 1 publication

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“… 38 To evaluate the clinical significance of these cytokines, we compared the serum cytokine levels in patients with TDI-OA and AECs at the time of diagnosis and AECs and found significant differences in the serum levels of MMP-9, IL-8, and VEGF. 39 Of these, MMP-9 was the most prominent cytokine, with the highest sensitivity (79.7%) and specificity (80.8%) using specific cutoff values. When the cytokines were combined to improve the sensitivity and specificity, the combination of MMP-9, VEGF, and IL-8 was the best, with the area under curve (AUC) value increasing to 0.822 (95% CI, 0.752 0.894; P <0.001) and the sensitivity and specificity changing to 82.6% and 75.8%, respectively.…”

Section: Serum Cytokines May Be Biomarkers For Tdi-oamentioning

confidence: 93%

“…A longitudinal study of patients with diisocyanate-induced asthma showed that inhaled steroid medication increased the BAL levels of MMP-9 and MMP-9/TIMP-1, which were inversely correlated with Th-2 type inflammation, suggesting a protective role of MMP-9 38. To evaluate the clinical significance of these cytokines, we compared the serum cytokine levels in patients with TDI-OA and AECs at the time of diagnosis and AECs and found significant differences in the serum levels of MMP-9, IL-8, and VEGF 39. Of these, MMP-9 was the most prominent cytokine, with the highest sensitivity (79.7%) and specificity (80.8%) using specific cutoff values.…”

Section: Serum Cytokines May Be Biomarkers For Tdi-oamentioning

confidence: 99%

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Biomarkers Predicting Isocyanate-Induced Asthma

Palikhe

Kim

Park

2011

Allergy Asthma Immunol Res

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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.

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Section: Serum Cytokines May Be Biomarkers For Tdi-oamentioning

confidence: 93%

Section: Serum Cytokines May Be Biomarkers For Tdi-oamentioning

confidence: 99%