Silicosis and autoimmunity

Our plain-English summary of Silicosis and autoimmunity, by S. Lee, H. Hayashi, H. Mastuzaki, et al (Current Opinion in Allergy and Clinical Immunology, 2017).

The study

• Authors: S. Lee, H. Hayashi, H. Mastuzaki, N. Kumagai-Takei, T. Otsuki
• Journal: Current Opinion in Allergy and Clinical Immunology
• Published: 2017;17(2):78-84
• Type of article: Review
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Of the various environmental, occupational, and medical substances that cause dysregulation of autoimmunity, the effects and causative mechanisms of silica particles and asbestos fibers are discussed in this review.

Recent Findings: With respect to silica, many epidemiological studies have shown a significant association between silica exposure and the occurrence of autoimmune diseases. Although the importance of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome as the initial immune reaction against silica particles has been identified, the mechanisms involved that lead to various autoimmune diseases in patients exposed to silica remain largely unknown. Silica can activate various immune cells and investigation of the associated imbalance of regulatory T cells, responder T cells as well as Th17 cells might be key in furthering our understanding of silica-induced autoimmune alterations. On the other hand, asbestos exposure shows less association with autoimmune diseases. However, interesting findings pertaining to the detection of antiendothelial and mesothelial cell antibodies in asbestos-exposed patients have been reported.

Summary: Taken together, further investigations may contribute in delineating the mechanisms involved in environmental factor-induced modification of autoimmunity.

In plain English

This article was a review, not a new study. The authors summarized published research, much from their own laboratory, on how silica particles and asbestos fibers affect autoimmunity, in which the immune system reacts against the body's own tissues. For silica, they cited epidemiological reports finding that the relative risk of rheumatoid arthritis was more than three times higher in silica-exposed people than in nonexposed people. They also reported that autoantibodies were frequently found in silicosis patients even though these patients did not show significant symptoms of related autoimmune diseases. They described their own earlier findings of an imbalance in silicosis, with responder T cells increased and regulatory T cells decreased. For asbestos, they described their earlier laboratory work, including experiments with chrysotile and a regulatory T cell-like cell line, pointing to reduced anti-tumor immunity. They also described other researchers' reports of autoantibodies against endothelial, fibroblast and mesothelial cells in mice and people exposed to Libby amphibole. The authors concluded that silica exposure makes patients prone to autoimmune diseases. They said disturbance of autoimmunity in asbestos-exposed people remains poorly understood.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on silica, asbestos and autoimmunity, drawing heavily on the authors' own earlier laboratory studies
• Who was studied: No new population was studied. The review covered earlier studies of silicosis patients and silica-exposed people (including the authors' own work on Japanese silicosis patients), asbestos-exposed patients with pleural plaque or malignant mesothelioma, cell lines, blood cells from healthy volunteers, mice, and a Libby amphibole-exposed population in Montana, USA.
• Exposure: Silica particles (silicosis) and asbestos fibers, including chrysotile in laboratory experiments and Libby amphibole (a mixture of amphibole fibers in contaminated vermiculite mined at Libby, Montana) in other researchers' studies
• Main results:
  • Citing earlier epidemiological reports, the authors stated that the relative risk of rheumatoid arthritis was more than three times higher in silica-exposed populations than in nonexposed populations. They also stated that systemic sclerosis, systemic lupus erythematosus and ANCA-related vasculitis were more common in silica-exposed people.
  • Autoantibodies (antinuclear antibodies, anti-Scl-70, anticentromere antibody, ANCA) were described as frequently found in silicosis patients, even though these patients did not show significant symptoms of related autoimmune diseases.
  • The authors' own earlier work found that a particular HLA gene variant (HLA-DQB1, allele 0402) was significantly more frequent in anti-Scl-70 antibody-positive silicosis patients than in negative patients or healthy controls.
  • The authors summarized their earlier findings as an imbalance in silicosis, with responder T cells increased and regulatory T cells decreased. They suggested this might make silicosis patients susceptible to autoimmune disease.
  • The authors' earlier asbestos work found reduced immune markers, including the natural killer cell receptor NKp46, in blood cells from asbestos-exposed patients with pleural plaque and malignant mesothelioma. Exposing a regulatory T cell-like cell line (MT-2) to asbestos enhanced regulatory T cell function. The authors interpreted these findings as reduced antitumor immunity.
  • Other researchers reported that asbestos exposure was linked to antiendothelial cell, antifibroblast and antimesothelial autoantibodies in a mouse model and in a Libby amphibole-exposed human population.
• The authors' conclusion: The authors concluded that silica exposure induces various autoantibodies and changes in T cells that make silica-exposed patients prone to autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and ANCA-related vasculitis. They said disturbance of autoimmunity in asbestos-exposed people remains poorly understood. In their view, asbestos exposure would lead to specific autoantibodies, but whether these influence lung fibrosis or autoimmune disorders remains to be determined by future studies.
• Limitations the authors state:
  • The authors stated that they had not themselves investigated changes in Th17 cells caused by silica exposure.
  • Some findings the authors described (serum cytokines in silicosis patients; cell cycle changes in the asbestos-exposed cell line) were preliminary data.
  • The authors stated that detailed investigations are still required to establish the cellular and molecular mechanisms of silica-induced changes in immune tolerance.

Topics

Medical terms in this study, explained in our Lexicon: Silicosis, Asbestos Exposure, Mesothelial Cells.

Related studies

• Silica exposure and altered regulation of autoimmunity — S. Lee, H. Matsuzaki, et al. (2014)
• Asbestos-induced autoimmunity in C57BL/6 mice — J.C. Pfau, J.J. Sentissi, et al. (2008)
• Silicosis and smoking strongly increase lung cancer risk in silica-exposed workers — N. Kurihara, O. Wada (2004)
• Silicosis among gemstone workers in South Africa: tiger's-eye pneumoconiosis — N.W. White, R. Chetty, et al. (1991)
• Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment — T. Otsuki, H. Matsuzaki, et al. (2016)
• Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice — A. Ferro, C.N. Zebedeo, et al. (2014)

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