Published By: Taylor & Francis
Contributors: Keith D. Salazar
Evaluation of Anti-Nuclear Antibodies and Kidney Pathology in Lewis Rats Following Exposure to Libby Amphibole Asbestos
ABSTRACT
The prevalence of anti-nuclear antibodies (ANA) and self-reported systemic autoimmune diseases were increased in residents of Libby, MT, as was the incidence of ANA in Lewis rats exposed to Libby amphibole (LA) asbestos. However, rats induced to develop rheumatoid arthritis (RA) did not develop autoantibodies associated with RA, nor was RA exacerbated by LA exposure, suggesting that increased ANA expression might be related to some other autoimmune process. Libby residents self-reported increased numbers of physician-diagnosed cases of systemic lupus erythematosus (SLE). Thus, the goal of this study was to determine if the increased incidence of ANA in Lewis rats exposed to LA is related to the development of SLE-like disease. Female Lewis rats were intratracheally instilled bi-weekly for 13 weeks with total doses of 0.15, 0.5, 1.5, or 5.0?mg of LA or 0.5 or 1.5?mg of a positive control fiber, amosite. ANA incidence was significantly increased in all asbestos dose groups, although no dose response was observed. The occurrence of proteinuria was increased in LA 0.5, LA 5.0, and amosite 0.5 dose groups; however, the microscopic appearance of the kidneys was normal, no binding of autoimmune complexes to glomerular surfaces was observed, and antibodies to double-stranded DNA were not elevated. Therefore, an increased prevalence of ANA in rats exposed to asbestos does not appear to correlate with disease markers typically observed in SLE. Analysis of ANA specificity for extractable nuclear antigens (ENA) determined that 98% of ENA+ samples were specific for the Jo-1 antigen. Autoantibodies to Jo-1 have been reported in participants with interstitial lung disease, suggesting that autoantibodies to Jo-1 may be a biomarker for asbestos-related pulmonary disease.
AUTHORS
Keith D. Salazar
Toxicity Pathways Branch, Integrated Risk Information System Division, National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency (USEPA) Washington, DCUSA
Carey B. Copeland
Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division
Charles E. Wood
Carcinogenesis Branch, Integrated Systems Toxicology Division
Judith E. Schmid
Research Cores Unit, National Health and Environmental Effects Research Laboratory (NHEERL), Office of Research and Development, USEPA Research Triangle Park, NCUSA
Robert W. Luebke
Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division