HLA-B*1301 as a biomarker for genetic susceptibility to hypersensitivity dermatitis induced by trichloroethylene among workers in China.(Research)(Report)

Trichloroethylene (TCE) is known as a major pollutant that affects both the occupational and general environment. It has been used as an industrial degreasing agent, solvent, and extraction agent for approximately a century. Alternatively, the general population may be exposed to TCE through contaminated drinking water or air. The target organs of TCE include the nervous system, 1iver, kidney, heart, and skin (Bruckner et al. 1989). Among the immunotoxicity end points, evidence for an effect of TCE was strongest for autoimmune disease. Studies in susceptible rodents have shown that TCE exacerbates underlying autoimmune disease, and supporting information comes from multiple human studies of scleroderma and exposure to organic solvents (National Research Council 2006).

Hypersensitivity dermatitis occurring in workers exposed to TCE is completely different from nonspecific skin irritation as a result of defatting action, and the serious consequences of TCE exposure have recently become one of the critical occupational health issues in Asia. The clinical manifestations of TCE exposure include generalized severe dermatitis, fever, abnormal liver function, jaundice, and lymphadenopathy. Skin lesions range from mild multiform erythema to lesions with increasing severity, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Huang et al. 2006). The literature published in English and ad hoc publications in local languages were reviewed in detail recently by Kamijima et al. (2007). Occurrences of the disease have been reported from the United States, Japan, Spain, Singapore, China, Korea, Thailand, and the Philippines. Most case reports from industrialized countries were published up to 1990, whereas cases from Asian industrializing countries were published later. In the past 10 years, an increasing number of cases of hypersensitivity dermatitis have been reported among TCE-exposed workers from electronic-element plants in Guangdong Province in southern China (Huang et al. 2002; Kamijima et al. 2007).

According to epidemiologic surveys in Guangdong Province, > 200 cases of hypersensitivity dermatitis have been diagnosed, with a prevalence rate of < 1% among TCE-exposed workers (Huang and Li 2006). Epidemiologic studies on patients with TCE-induced hypersensitivity dermatitis reveal that the latency ranges from 6 to 89 days, and a no dose-response relationship was observed (Li et al. 2006). Furthermore, the patch test using TCE and/or its oxidative metabolites among victims was positive (Huang et al. 2002).

The incidence of hypersensitivity and autoimmune diseases in industrialized countries has steadily increased over the past three decades (Bach 2002), and these diseases are not evenly distributed among countries, regions, or ethnic groups. However, the degree to which genetic and environmental factors influence susceptibility to hypersensitivity and autoimmune diseases is not well defined. One main feature of occupational diseases is relatively defined causative factors, so studies on these diseases are helpful in identifying the role of genetic factors.

One of the best ways to prevent occupational hypersensitivity disease is to identify susceptible biomarkers to use in screening employees before exposure. To date, however, there are no available biomarkers for predicting who among TCE-exposed workers is at high risk of developing hypersensitivity dermatitis. Other factors associated with the disease remain unknown except for human herpes virus 6 reactivation (Huang et al. 2006). The genomic region of human leukocyte antigen (HLA) at chromosomal position 6p21 encodes the six classical HLA genes and many other genes that have important roles in the regulation of the immune system as well as in some fundamental cellular processes. The classical class I (HLA-A, HLA-B, and HLA-C) and class II molecules (HLA-DR, HLA-DQ, and HLA-DP) are involved in the control of immune-response mediation of antigen presentation to the T lymphocytes, and play a central role in the immune system by presenting peptides (Shiina et al. 2004). The HLAs are characterized by an extensive degree of allelic polymorphism; strong associations between hypersensitivity or autoimmune disease and certain …