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AUTOANTIBODY PROFILES OF AN ASBESTOSEXPOSED POPULATION, pp. 71 - 94 $100.00
Authors:  Jean C. Pfau, David J. Blake and Marvin J. Fritzler
Abstract:
Asbestos exposure is associated with autoimmune responses including increased
serum immunoglobulins, positive autoantibody tests and immune complex deposition.
Occupational and environmental asbestos exposures continue to occur world-wide,
making this a current human health issue. The premise that asbestos exposure exacerbates
autoimmunity is supported by recent studies from an asbestos exposed population in
Libby, Montana, USA. Residents of Libby have experienced significant exposures to
amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the
community over several decades. This community exhibits higher frequencies of positive
anti-nuclear antibody (ANA) tests compared to an unexposed control population and
what would be expected based on epidemiological data.
Systemic autoimmune diseases are characterized by autoantibody profiles that
correspond to specific sets of intracellular components. These profiles can be used to help
predict disease, establish a diagnosis as well as assess clinical progression. At this time, it
is not known whether a discrete clinical or sub-clinical autoimmune entity is associated
with amphibole asbestos exposure. However, asbestos exposure leads to clinical
manifestations similar to systemic lupus erythematosus (SLE) in asbestos exposed mice.
Therefore, we hypothesized that features of certain autoimmune diseases may be
associated with asbestos exposure in humans. The purpose of this study was to determine
whether a serological signature exists in this asbestos-exposed population, and to compare this profile with other known systemic autoimmune disease autoantibody
profiles.
Our results indicate that autoantibodies from individuals exposed to amphibole
asbestos primarily recognize chromatin, histone and Ro52, similar to patients with
systemic lupus erythematosus (SLE). Anti-dsDNA and anti-Ro52 antibodies are also
generated in a murine model of asbestos induced autoimmunity, which suggests that
asbestos may drive similar immune phenomena in both humans and mice. In addition, we
show that an unexpected number of subjects expressed the Scl-topoisomerase I (topo I:
also referred to as Scl-70) antibody, typically seen in scleroderma. The subjects with antitopo
I tended to have higher levels of asbestos exposure and more severe lung disease
compared to those without topo I, whereas there was no association with exposure or
lung disease among people with anti-RNP (antibodies to ribonucleoprotein, common in
SLE). Finally, we show that some Libby serum samples contained antibodies that bound
fibroblasts, a phenomenon that is also seen in scleroderma. By comparison, neither
rheumatoid factor (RF) nor anti-cyclic citrullinated peptide (CCP), markers for
rheumatoid arthritis (RA), was substantially elevated in the Libby sample set. This
information could be extremely valuable for improved screening of exposed populations.
In addition, certain autoantibody profiles may serve as diagnostic or prognostic markers
relative to asbestos exposure. 


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AUTOANTIBODY PROFILES OF AN ASBESTOSEXPOSED POPULATION, pp. 71 - 94