Analysis of autoantibody profiles in two asbestiform fiber exposure cohorts

Our plain-English summary of Analysis of autoantibody profiles in two asbestiform fiber exposure cohorts, by J.C. Pfau, C. Barbour, B. Black, et al (Journal of Toxicology and Environmental Health. Part a, 2018).

The study

• Authors: J.C. Pfau, C. Barbour, B. Black, K.M. Serve, M.J. Fritzler
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2018;81(19):1015-1027
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

An increased risk for Systemic Autoimmune Diseases (SAID) was reported in the population of Libby, Montana, where extensive exposure to asbestiform amphiboles occurred through mining and use of asbestiform fiber-laden vermiculite. High frequencies of antinuclear autoantibodies (ANA) were detected in individuals and mice exposed to Libby Asbestiform Amphiboles (LAA). Among the 6603 individuals who have undergone health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), the frequencies of rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and systemic sclerosis are significantly higher than expected prevalence in the United States. While these data support the hypothesis that LAA can trigger autoimmune responses, evidence suggests that chrysotile asbestos does not. Serological testing was therefore performed in subjects exposed to LAA or predominantly chrysotile (New York steamfitters) using multiplexed array technologies. Analyses were performed in order to determine a) autoantibody profiles in each cohort, and b) whether the two populations could be distinguished through predictive modeling. Analysis using perMANOVA testing confirmed a significant difference between autoantibody profiles suggesting differential pathways leading to autoantibody formation. ANA were more frequent in the LAA cohort. Specific autoantibodies more highly expressed with LAA-exposure were to histone, ribosomal P protein, Sm/Ribonucleoproteins, and Jo-1 (histidyl tRNA synthetase). Myositis autoantibodies more highly expressed in the LAA cohort were Jo-1, PM100, NXP2, and Mi2a. Predictive modeling demonstrated that anti-histone antibodies were most predictive for LAA exposure, and anti-Sm was predictive for the steamfitters' exposure. This emphasizes the need to consider fiber types when evaluating risk of SAID with asbestos exposure.

In plain English

This cross-sectional study compared autoantibodies (antibodies against the body's own components, such as proteins and DNA) in blood from two asbestos-exposed groups. The first was 397 current or former residents of Libby and Troy, Montana, exposed to Libby asbestiform amphiboles (LAA) from vermiculite. The second was 87 New York steamfitters, all men, whose exposure the authors described as predominantly chrysotile. Antinuclear antibody (ANA) tests were positive in 43% of the Libby group and 23% of the steamfitters. On questionnaires, 30 Libby subjects (7.6%) and 1 steamfitter (1.1%) reported a physician-diagnosed systemic autoimmune disease. Overall autoantibody profiles differed significantly between groups. A statistical model told the groups apart with a validation score (AUC) of 0.967. Higher anti-histone levels pointed to the Libby group, higher anti-Sm levels to the steamfitters. However, only 3 steamfitters and 5 Libby subjects reached the clinical cut-off for positive anti-Sm. No link between antibodies and exposure estimates, available for 268 Libby subjects and 35 steamfitters, was detected. Smoking history was missing for the steamfitters. The authors concluded that fiber type should be considered when evaluating autoimmune risk from asbestos.

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: Cross-sectional comparison of blood autoantibody tests between two asbestos-exposed cohorts, with statistical modeling (random forest) to predict cohort membership
• Who was studied: 484 serum samples: 397 from current or former residents of Libby and Troy, Montana, screened or treated at the Center for Asbestos Related Diseases (158 women, 239 men), and 87 male members of the New York State steamfitters union screened through the Icahn School of Medicine at Mt Sinai; all subjects were over 18
• Exposure: Libby asbestiform amphiboles (LAA) from vermiculite mining and use, through work or residence (53.3% mostly occupational, 46.7% mostly environmental/residential), compared with steamfitters' occupational exposure (100% occupational), which the authors describe as predominantly chrysotile, from gaskets, valves and pumps
• Main results:
  • ANA tests were positive in 43% of the LAA cohort and 23% of the Steamfitters cohort (p = 0.001, Fisher's exact test); among men only, 42% versus 23% (p = 0.01)
  • Physician-diagnosed systemic autoimmune disease (RA, SLE, SSc, sarcoidosis), reported in questionnaires: 30 cases (7.6%) in the LAA cohort and 1 case (1.1%, sarcoidosis) in the Steamfitters cohort (p = 0.03)
  • perMANOVA testing found a significant overall difference in autoantibody profiles between the two cohorts
  • A classification model based on the extractable nuclear antibody (ENA) panel distinguished the LAA cohort from the Steamfitters cohort with a validation AUC of 0.967
  • In the model, higher anti-histone values were associated with a higher probability of belonging to the LAA cohort, and higher Sm values with the Steamfitters cohort
  • Only 3 steamfitters and 5 Libby subjects had anti-Sm values reaching the clinical cut-off for a positive test; none of the Sm-positive steamfitters had a systemic autoimmune disease diagnosis, while 3 of the Sm-positive Libby subjects did
  • Within each cohort, among subjects with available exposure data (N = 268 in the LAA cohort, N = 35 steamfitters), no associations were detected between antibody levels and exposure measures, which were scoring matrices based on self-reported jobs and activities
• The authors' conclusion: The authors concluded that the two cohorts differed detectably in overall autoantibody frequency and in the specific autoantibodies expressed. They stated that this emphasizes the need to consider fiber type when evaluating risk of autoimmune outcomes attributed to asbestos exposure.
• Limitations the authors state:
  • Smoking history was missing for the Steamfitters cohort
  • The two cohorts' exposure scoring matrices were different, so exposure values could not be compared between cohorts
  • Data on latency between start of work and the study were not available for many subjects

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Asbestiform, Amphibole Group, vermiculite, Chrysotile, Asbestos Exposure.

Related studies

• Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles — N. Yanamala, E.R. Kisin, et al. (2018)
• Asbestos-associated mesothelial cell autoantibodies promote collagen deposition in vitro — K.M. Serve, B. Black, et al. (2013)
• Carving of non-asbestiform tremolite and the risk of lung cancer: a follow-up mortality study in a historical nephrite processing cohort — H.Y. Yang, R.H. Shie, et al. (2013)
• Libby amphibole-induced mesothelial cell autoantibodies bind to surface plasminogen and alter collagen matrix remodeling — R. Hanson, C. Evilia, et al. (2016)
• Case series: rheumatological manifestations attributed to exposure to Libby Asbestiform Amphiboles — R. Diegel, B. Black, et al. (2018)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)

Browse more research in Journal of Toxicology and Environmental Health. Part a, or return to medical research.