Unmasking the mysteries of chronic beryllium disease
New tests identify sensitivity, genetic susceptibility
Beryllium is a unique lightweight metal used in nuclear
weapons and, in the commercial sector, for telescope
mirrors, golf clubs and a variety of other applications.
While solid beryllium and beryllium alloys are safe, fine
particulate beryllium is hazardous if inhaled.
In certain individuals, breathing microscopic beryllium particles can
lead to Chronic Beryllium Disease (CBD), sometimes called berylliosis.
CBD is a long-duration, allergic-type lung response that can make the
sufferer abnormally weak and is sometimes fatal.
Research into beryllium health effects in the Bioscience Division at Los
Alamos National Laboratory center on identifying worker sensitivity
and increased risk caused by genetic factors. Only a small percentage
of people exposed to beryllium become sensitized to it, meaning they
experience an immune-system reaction to exposure. In addition, it
appears that not everyone who is sensitized develops CBD.
A team led by Bioscience Division researcher Babs Marrone has devised
an improved Lymphocyte Proliferation Test, or LPT, a blood test that
can identify sensitized individuals. The researchers also have found
genetic markers that indicate increased susceptibility.
The new test, called
the Immuno-LPT, takes
advantage of the fact that
both sensitization and
CBD are immune-system
responses. Using flow
cytometry, a laser-based, cell-analysis technique
developed at Los Alamos, researchers can detect a
proliferation of a specific
white blood cell, or
lymphocyte, known as aCD4+cell, that forms in response to beryllium. Results suggest that because CD4+ cell proliferation in people sensitized to beryllium matches the response in people who have CBD, the
Immuno-LPT may be quite accurate in predicting the development of CBD.
Because some individuals develop sensitivity and disease when exposed to only miniscule
amounts of beryllium, while others with high levels of exposure never get sensitized or develop
CBD, scientists wondered if there could be a genetic risk factor.
"Our research has shown that the majority of individuals with CBD, or with a CD4+ response to
beryllium, have rare variations of a gene on chromosome 6 containing what is known as a 'Glu69' marker," said Marrone. "We looked closely at the variations around the marker, and we found
other contributing genetic factors that help us pinpoint those who are at increased risk."
Because these genetic differences are inherited and not caused by beryllium exposure, researchers
could use the genetic markers to identify individuals with greater susceptibility to develop beryllium disease.
All genetic-marker information must be kept confidential, said Marrone. And taking the test must
be the decision of the workersówith their informed consent. Given that, the Lab would like to
offer the genetic-marker test to more than 3,000 current and former Lab employees who either
worked with beryllium or may have had incidental exposure.
Ethical and legal issues must be carefully considered in any genetic testing program, either at the
Lab or in industry, according to Marrone. "We want to get the best possible information to the
workers so that they can then make informed decisions about their work situation," she said. "At
the same time, we must ensure that information from genetic testing does not lead to any kind of
Marrone and her colleagues continue to work with industrial hygienists, physicians, environmental scientists, chemists and health physicists to understand better how beryllium damages the
immune system, with the ultimate goal of a cure for beryllium disease. Experts in legal and ethical
issues also seek to integrate new information about genetic markers into beryllium medical surveillance practices.
The Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time.