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Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study.

ABSTRACT: Occupational exposure to trichloroethylene (TCE) causes a systemic skin disorder with hepatitis known as TCE hypersensitivity syndrome (TCE-HS). Human Leukocyte Antigen (HLA)-B*13:01 is its susceptibility factor; however, the immunological pathogenesis of TCE-HS remains unknown. We herein examined the hypothesis that autoantibodies to CYP2E1 are primarily involved in TCE-HS. A case-control study of 80 TCE-HS patients, 186 TCE-tolerant controls (TCE-TC), and 71 TCE-nonexposed controls (TCE-nonEC) was conducted to measure their serum anti-CYP2E1 antibody (IgG) levels. The effects of TCE exposure indices, such as 8-h time-weighted-average (TWA) airborne concentrations, urinary metabolite concentrations, and TCE usage duration; sex; smoking and drinking habits; and alanine aminotransferase (ALT) levels on the antibody levels were also analyzed in the two control groups. There were significant differences in anti-CYP2E1 antibody levels among the three groups: TCE-TC > TCE-HS patients > TCE-nonEC. Antibody levels were not different between HLA-B*13:01 carriers and noncarriers in TCE-HS patients and TCE-TC. The serum CYP2E1 measurement suggested increased immunocomplex levels only in patients with TCE-HS. Multiple regression analysis for the two control groups showed that the antibody levels were significantly higher by the TCE exposure. Women had higher antibody levels than men; however, smoking, drinking, and ALT levels did not affect the anti-CYP2E1 antibody levels. Anti-CYP2E1 antibodies were elevated at concentrations lower than the TWA concentration of 2.5 ppm for TCE exposure. Since HLA-B*13:01 polymorphism was not involved in the autoantibody levels, the possible mechanism underlying the pathogenesis of TCE-HS is that TCE exposure induces anti-CYP2E1 autoantibody production, and HLA-B*13:01 is involved in the development of TCE-HS.

SUBMITTER: Nakajima T

PROVIDER: S-EPMC9352743 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study.

Nakajima Tamie T Wang Hailan H Yuan Yuan Y Ito Yuki Y Naito Hisao H Kawamoto Yoshiyuki Y Takeda Kozue K Sakai Kiyoshi K Zhao Na N Li Hongling H Qiu Xinxiang X Xia Lihua L Chen Jiabin J Wu Qifeng Q Li Laiyu L Huang Hanlin H Yanagiba Yukie Y Yatsuya Hiroshi H Kamijima Michihiro M

Archives of toxicology 20220628 10

Occupational exposure to trichloroethylene (TCE) causes a systemic skin disorder with hepatitis known as TCE hypersensitivity syndrome (TCE-HS). Human Leukocyte Antigen (HLA)-B*13:01 is its susceptibility factor; however, the immunological pathogenesis of TCE-HS remains unknown. We herein examined the hypothesis that autoantibodies to CYP2E1 are primarily involved in TCE-HS. A case-control study of 80 TCE-HS patients, 186 TCE-tolerant controls (TCE-TC), and 71 TCE-nonexposed controls (TCE-nonEC) ...[more]

PMID: 35763063

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Project description:BackgroundOccupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver cancer; however, TCE's mode of action for development of these diseases in humans is not well understood.MethodsNon-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppma)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population.ResultsMetabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10-5), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = -1.6, P-value = 0.0043), taurine (β = -2.4, P-value = 0.0011) and chenodeoxycholic acid (β = -1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations.ConclusionsHigh-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology.

Project description:ObjectivesTrichloroethylene (TCE) is a carcinogen that has been causally linked to kidney cancer and possibly other cancer sites including the liver and lymphatic system. Its use in China has increased since the early 1990s due to the growing metal and electronic industries. We aimed to summarize the major sources of occupational exposure to TCE over time in China.MethodsOccupational TCE exposure assessments were extracted from both the Chinese and English scientific literature, as well as from industrial hygiene surveys performed in Guangdong, Tianjin, and Hong Kong. Weighted mean concentrations were summarized by occupation and industry.ResultsWe extracted over 12,412 measurements from 55 industries and 35 occupations across China since 1976, of which at least 201 were from case reports. More than half of the measurements were derived from 4 industries, including "manufacture of footwear" (29%), "manufacture of electronic components and boards" (17%), "manufacture of games and toys" (14%), and "manufacture of fabricated metal products, except machinery and equipment" (13%). Several occupations, including "electronic-equipment assemblers," "metal-, rubber-, and plastic-products assemblers," "metal finishing-, plating-, and coating-machine operators," "precision-instrument makers and repairers," "printing-machine operators," and "ore and metal furnace operators" were identified as having high risks of TCE exposure, with either pooled weighted mean task-based or full-shift concentrations over 150 mg/m3 over the years. TCE exposure levels varied across different occupations and changed over time. In 1990 and earlier, 1991 to 2000, the exposure levels were at their highest with pooled weighted mean task-based concentrations of 202.8 and 242.9 mg/m3, respectively. Subsequently, the level decreased to 118.7 mg/m3 from 2001 to 2010 before increasing again to 216.0 mg/m3 from 2011 onwards. This overall trend was also observed for "electronic-equipment assemblers" and "metal finishing-, plating-, and coating-machine operators." However, for "precision-instrument makers and repairers," the exposure levels consistently declined over the years.ConclusionsOver the past few decades, degreasing-related occupations, such as "electronic-equipment assemblers" and "metal finishing-, plating-, and coating-machine operators" have been consistently identified as being at high risk of significant TCE exposure and continued to warrant attention. Identifying high-risk industries and occupations can inform the development of targeted interventions and regulations to mitigate TCE exposure. Furthermore, enhancing the quality and coverage of exposure measurement data in occupational settings will advance epidemiological investigations in occupational health.

Dataset Information

Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study.

Publications

Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study.

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