Therefore, additional initiatives for even more elucidation should follow. strong course=”kwd-title” Keywords: asthma, hereditary polymorphism, HLA, particular IgE, particular IgG, toluene diisocyanate Although a lot more than 300 causative agents Neuronostatin-13 human of asthma have already been reported, isocyanate, specifically toluene diisocyanate (TDI), may be the most prevalent reason behind occupational asthma worldwide. system may be involved with airway irritation. Neutrophil activation and oxidant/antioxidant-related systems were suggested also. Bottom line The pathogenic system of TDI-induced asthma is certainly complicated as different humoral and mobile systems are mixed and involved in different ways on a person basis. Therefore, extra efforts for even more elucidation should follow. solid course=”kwd-title” Keywords: asthma, hereditary polymorphism, HLA, particular IgE, particular IgG, toluene diisocyanate Although a lot more than 300 causative agencies of asthma have already been reported, isocyanate, specifically toluene diisocyanate (TDI), may be the most widespread reason behind occupational asthma world-wide. Although incidences are mixed with regards to the forms and types of isocyanate, it is generally reported that 5% of TDI-exposed workers could develop TDI-induced asthma [1]. The annual incidence rate of isocyanate-induced asthma was 1.8% in TDI production facilities [2]. The follow-up study on TDI-induced asthma demonstrated that 50% of TDI-induced asthmatic patients had experienced persistent asthmatic symptoms even after cessation of exposure to isocyanate [3]. The pathogenic mechanism of occupational asthma is complicated by the fact that both immunologic and non-immunologic pathways may be involved, depending upon the causative agent [3-6]. In addition, several environmental factors, including the nature of the causative agent and the level and mode of exposure, affect the pathogenesis of occupational asthma. In cases involving low-molecular-weight chemicals, particularly TDI, both immunoglobulin E (IgE)- and non-IgE-mediated pathways have been implicated [3-7]. Several studies examining the role Neuronostatin-13 human of specific IgG antibodies against isocyanate have yielded controversial results [3-5]. This review summarizes our current understanding of the pathogenic mechanisms of TDI-induced asthma and outlines a series of questions that must be addressed to further our understanding of the pathogenesis of isocyanate-induced asthma. Genetic mechanisms of isocyanate-induced asthma HLA allele studies A European study of 142 patients with TDI-induced asthma and 50 asymptomatic exposed controls demonstrated that HLA class I alleles were not significantly associated with TDI-induced asthma [8]. However, a comparison of TDI-induced asthma subjects with asymptomatic exposed controls Neuronostatin-13 human using high-resolution techniques demonstrated that 1 HLA class II allele, DQB1*0503, and 1 haplotype, DQB1*0201-0301, were significantly associated with TDI-induced asthma [9,10]. These results were later refuted by data from a German population, showing no association between the disease and the HLA class II allele [11]. In a Korean population, we used a high-resolution sequencing method to compare a number of HLA class I and II alleles in 55 TDI-induced asthma patients with those in 47 asymptomatic exposed subjects and 95 unexposed healthy nonatopic controls; the HLA haplotype DRB1*15-DPB1*05 was found to be a susceptibility marker for the development of TDI-induced asthma among exposed workers [12]. To resolve the differences between our results and those of the other groups mentioned previously, additional studies using a larger cohort of TDI-induced asthma patients in different ethnic groups are needed. Genetic polymorphism studies The genes for glutathione S-transferase [13] and N-acetyltransferase [14] are believed to confer susceptibility to, or protection against, TDI-associated asthma. Bernstein et al [15] suggested a gene-to-environment interaction with em IL4RA, CD14 /em , and em IL13 /em . Based on studies showing the involvement of neurogenic inflammation in TDI-induced asthma, we used a single base extension to screen for 2 single-nucleotide polymorphism of neurokinin 2 receptor (NK2R) gene, 7853C T and 11424G A, in 70 patients with TDI-induced occupational asthma, 59 asymptomatic exposed controls, and 93 unexposed healthy controls [16]. No significant differences were noted in the allele, genotype, or haplotype frequencies of the 2 2 single-nucleotide polymorphism among the 3 groups. However, those TDI-exposed workers with the NK2R 7853CC genotype had higher serum levels of vascular endothelial growth factor than did those with the CT or TT genotype. We Rabbit Polyclonal to MSH2 speculate that the NK2R 7853CC genotype may contribute to an increase in the serum level of vascular endothelial growth factor, resulting in airway inflammation after exposure to TDI. Additional studies are needed to investigate other candidate genes and gene-to-environment interactions in people of various ethnicities. Role of specific IgE antibodies against isocyanate in occupational asthma Several investigators have detected IgE antibodies specific for TDI-human serum albumin (HSA) conjugate in the sera of workers showing a positive bronchial challenge response to TDI, with a reported prevalence of 0% to 50% of workers [3,4,7]. Maestrelli et al [17] demonstrated that the bronchial mucosa of TDI-induced asthma patients contained increased numbers of cells expressing interleukin 5 (IL-5) and IL-4. Similarly, we found that 13% of TDI-induced asthma patients had specific IgE antibodies, [18] although subsequent enzyme-linked immunosorbent assay (ELISA) inhibition tests using 3 different TDI-HSA conjugates prepared under the same conditions revealed different inhibition patterns [19]. We recently demonstrated that the sensitivity of the specific IgE antibodies could be increased to 44% when a volatile type of TDI-HSA conjugate was.