Case series: rheumatological manifestations attributed to exposure to Libby Asbestiform Amphiboles

Abstract

An increased risk for Systemic Autoimmune Diseases (SAID) has been reported in Libby, Montana, where extensive exposures to fibrous amphiboles occurred due to mining and use of asbestos-laden vermiculite. In addition, positive antinuclear autoantibody tests are associated with exposure to Libby Asbestiform Amphiboles (LAA) in both humans and mice. Among 6603 subjects who underwent health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), 13.8% were diagnosed with an autoimmune disease, with prevalence values for the most common SAID being significantly higher than expected in the United States. Among the CARD screening population, serological and clinical profiles are diverse, representing symptoms and autoantibodies reflective of systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis and other rheumatic syndromes including Undifferentiated Connective Tissue Disease (UCTD). Based upon screening of medical records by physicians with rheumatology expertise, the evolving nature of rheumatological disease in these patients is often atypical, with mixed diagnostic criteria and with a 1:1 male-to-female ratio. Through the Libby Epidemiology Research Program, cases were identified that illustrate clinical autoimmune outcomes with LAA exposure. Our goal was to better characterize SAID in Libby, MT in order to improve recognition of autoimmune outcomes associated with this exposure. In view of recent discoveries of widespread exposure to fibrous minerals in several areas of the U.S. and globally, it is critical to evaluate rheumatologic manifestations in other cohorts so that screening, surveillance and diagnostic procedures are able to detect and recognize potential autoimmune outcomes of asbestos exposure.

Analysis of autoantibody profiles in two asbestiform fiber exposure cohorts

“…The results support and extend our previous studies, which reported elevated frequencies and titers of ANA in the Libby population, as well as an increased risk for SLE, SSc, RA, and sarcoidosis (Noonan, et al 2006, Pfau, et al 2005, Diegel, et al 2018). Exposure to LAA was demonstrated to be associated with an elevated frequency of positive ANA tests in non-autoimmune prone mice and rats as well (Ferro, et al 2013, Pfau, et al 2008, Salazar, et al 2012).…”

“…In 2006, a case-control study of self-reported SLE patients, nested within a medically screened general population cohort in Libby, MT, showed a more than 4-fold elevated risk for SLE associated with a history of greater LAA exposure via multiple environmental pathways (Noonan, et al 2006). Among the 6603 individuals who have undergone health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), the frequencies of RA, SLE, sarcoidosis, and SSc are significantly higher than the published expected prevalence for these diseases in the United States (Diegel, et al 2018). However, unlike investigations of crystalline silica (Cooper, et al 2010, Pollard 2016), there are no apparent large cohort analyses of risk for SAID that establish asbestos or asbestiform structures as a trigger for autoimmunity.…”

The Effects of Asbestos Fibers on Human T Cells

“…In this regard, some groups are conducting research using asbestos-exposed individuals or animal models of autoimmune diseases, and it is expected that the results will be forthcoming. Th17 cells seem to be more strongly involved in the breakdown of self-tolerance rather than anti-tumor immunity [ 56 , 57 , 58 ]. This area requires extensive further investigation.…”

Perspective: The Lung, Particles, Fibers, Nanomaterials, and Autoimmunity

“…Several different cohorts including Libby, Montana (73), Wittenoom, Western Australia (74), and Biancavilla, Sicily (75), have linked autoantibodies, including ANA, to asbestos exposure. Studies of the communities of Libby and Troy in Montana have found that almost 14% have been diagnosed with an autoimmune disease other than diabetes (76,77) and mortality to autoimmune diseases is higher than expected (78). However, a causal role for asbestos exposure in autoimmune disease has not been established due to study limitations (4), and other confounders, including the possibility of concurrent silica and asbestos exposures (2), and smoking history (79).…”

“…Autoimmune diseases associated with Libby Asbestiform Amphibole (LAA) exposure include SLE, SSc, and RA (76,78). ANA are common and include autoantibodies against dsDNA, SS-A/Ro52, Scl70, Sm, and RNP (76). Anti-mesothelial cell antibodies, and ANA, have been linked to pleural abnormalities (85).…”