HLA class II alleles in isocyanate-induced asthma.

Abstract

Studying genetic factors that control human immune responsiveness may further our understanding of specific types of asthma in which the role of immune factors is uncertain to date. HLA Class II gene products are involved in the control of immune responses. Therefore, we investigated whether HLA Class II genetic markers contribute to susceptibility or resistance to isocyanate-induced asthma (IAA) in exposed workers. We collected venous blood samples from two groups of unrelated white adults: (1) patients with isocyanate-induced asthma documented by a positive inhalation challenge; and (2) exposed individuals with no history of IAA. The second exon of DQA1, DQB1, DPB1, and DRB genes was selectively amplified by the polymerase chain reaction (PCR) method. HLA typing was carried out by the PCR-RFLP method, which allowed discrimination of most HLA DQA1, DQB1, DPB1, and DRB alleles. No significant difference was found in the distribution of DPB1 alleles between patients and control subjects. Allele DQB1*0503 and allelic combination DQB1*0201/0301 were associated with susceptibility to the disease. Conversely, allele DQB1*0501 and the DQA1*0101-DQB1*0501-DR1 haplotype conferred significant protection to exposed healthy control subjects. Our results are consistent with the hypothesis that immune mechanisms are involved in isocyanate-induced asthma and that specific genetic factors may increase or decrease the risk of developing IAA in exposed workers.

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).…”

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

“…Unlike other risk factors for biphasic reactions (that include more rapid onset of anaphylaxis delayed use of epinephrine, low doses of epinephrine, etc), mast cell diseases have never been studied as such. 4 We describe 2 patients with intraoperative anaphylaxis who were diagnosed postoperatively as having mastocytosis.…”

“…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.…”