Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57

Abstract

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma.We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n=30); 2) exposed subjects with no history of TDI-induced asthma (n=12); and 3) normal subjects not exposed to TDI (n=126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method.Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1*0503 and a negative association with HLA-DQB1*0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1*0503 and valine in DQB1*0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls.Our results confirm the hypothesis that HLA-DQB1*0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.

Occupational asthma: a review.

“…In workers with exposure to diisocyanates, HLA-DQB1*0503 and DQB1*0201/0301 alleles are associated with asthma, whereas HLA-DQB1*O501 and DQA1*0101-DQB1*0501-DR1 appear to be protective (29). The alleles, HLA-DQB1*0503 and HLA-DQB1*0501, differ at residue 57 for a single amino acid, aspartic acid in DQB1*0503 and valine in DQB1*0501, suggesting that residue 57 may be a potentially critical location in the development of asthma (30). Associations with MHC proteins have also been described in acid anhydride-induced asthma (31), in platinum salts-induced asthma, and in red cedar-induced asthma (32).…”

HLA CLASS II ALLELE AND IgG SENSITIZATION TO METHYLENE DIISOCYANATE IN EXPOSED WORKERS

“…Although it is well known that mastocytosis can lead to the development of non-IgE-mediated severe intraoperative reactions, without standard guidelines for the intraoperative management of these patients, premedication consisted of antihistamines, corticosteroids, and disodium cromoglycate by means of nebulization and the oral route; stress-reducing ansiolitics were administered, and safer anesthetic drugs were used. 7,8 No undesired intraoperative or postoperative reactions occurred.…”

“…3 For TDI-OA, the pathogenic mechanism is unknown, and there have been several reports on the genetic susceptibility of Italian 4,5,7 and Korean 6 populations.…”

Review of the occupational exposure to isocyanates: Mechanisms of action

“…Bernstein et al 50) reported evidence that the involvement of the TCR Vβ repertoire expression increased the expression Vβ1 and Vβ5 after in vitro stimulation in patients who were exposed to diisocyanate. Bignon et al 51) , Balboni et al 52) and Mapp et al 53) studied the HLA class II alleles' contribution to susceptibility or resistance to isocyanate-induced asthma in exposed workers. They reported that allele DQB1*0503 and the allele combination DQB1*0201/0301 were associated with susceptibility to the disease.…”