Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Abstract

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p=0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects (p=0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.

Figure 1

Anti-Mesothelial Cell antibodies. A. Visualization of surface binding of human serum autoantibodies. Met-5A cells grown on chamber slides were plated, fixed and stained exactly as for the cell-based ELISA, but the secondary antibody was anti-Mouse FITC and nuclei were counterstained with DAPI. Image on the left is stained with serum cleared of IgG using Protein G; image on the right is stained with uncleared serum from a subject from Libby. B. Optical density scores for mesothelial cell autoantibodies (MCAA) in Libby and Missoula serum samples. Cell-based ELISA analysis of Libby and Missoula serum samples revealed a significant difference between the average absorbance levels for MCAA in Missoula and Libby MT populations (p<0.001). Positive samples were defined as any having absorbance readings higher than three standard deviations above the mean value of the Missoula samples (Abs >1.38, dotted line). The 23 Libby samples were determined to be MCAA positive based on this definition.

Figure 2

Prevalence of pulmonary radiographic abnormalities (lesions) including 95% confidence intervals (indicated with bars) among individuals from Libby MT with and without autoantibodies to nuclear antigens (ANA). There were 76 ANA positive subjects, and 48 ANA negative subjects analyzed.

Figure 3

Prevalence of pulmonary radiographic abnormalities (lesions) including 95% confidence intervals (indicated with bars) among mesothelial cell autoantibodies (MCAA) positive and negative individuals from Libby. There were 23 MCAA positive and 101 MCAA negative samples.