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Environmental Factor, March 2012

Council talks highlight human studies of autoimmunity and immunotoxicity

By Anshul Pandya

Fred Miller, M.D., Ph.D.

Describing autoimmune disease as “a rather neglected area … that is very near and dear to my heart,” Miller argued that identifying mutually exclusive, stable phenotypes for individual diseases can help clinicians better identify, treat, and ultimately prevent them. (Photo courtesy of Steve McCaw)

Philippe Grandjean, M.D.

Grandjean concluded by expressing his gratitude for NIEHS support for work on what he called a silent pandemic. “If we have made a small contribution to the science and perhaps to public policy, it’s to a great extent because you have supported us.” (Photo courtesy of Steve McCaw)

Members of the National Advisory Environmental Health Sciences Council heard two exciting scientific presentations at their meeting Feb. 16 at NIEHS. The first, by Acting Director of the NIEHS Clinical Research Program, Fred Miller, M.D., Ph.D., focused on environmental and genetic links to autoimmune disease. The second, by NIEHS grantee Philippe Grandjean, M.D., (http://www.hsph.harvard.edu/faculty/philippe-grandjean/)  of the Harvard School of Public Health, discussed immunotoxicity in a population of children exposed to contaminants in a seafood-based diet.

Miller — autoimmune disease, when the body turns upon itself

Miller opened his talk by telling the audience, “Autoimmune diseases, like multiple sclerosis, lupus, scleroderma, myasthenia gravis, and myositis syndromes, have major public health implications.” Although, individually, most of these 80 diseases are rare, autoimmune diseases collectively affect some 22 million people in the U.S., with rates on the rise.

According to Miller, environmental factors implicated in autoimmune diseases include infectious agents such as bacteria and viruses, as well as non-infectious agents such as drugs, biologics, foods, ultraviolet radiation, and occupational exposures. He added that for some diseases the onset varies seasonally, as well as by geographic location, which also suggests an important role for environmental exposures.

Miller elaborated on the complex interplay between environmental factors and genes in the pathophysiology of various autoimmune diseases. “Defining the environmental and genetic associations for a specific autoimmune disease remains a challenge,” he explained. “While environmental factors can activate a gene or set of genes which may trigger an autoimmune disease, it is also possible that the activation of certain genes may also have a protective effect for some autoimmune diseases.”

Translating presentation into treatment

Miller specifically focused on a group of autoimmune disorders called the myositis syndromes, which are characterized by chronic inflammation of the muscles. His group uses epidemiological surveys, molecular genetic studies, and clinical evaluations to investigate the pathogenesis of the myositis syndromes, as well as to develop improved clinical tools for the assessment of innovative therapies for treating these life-threatening disorders.

Characterizing different forms of myositis, Miller explained, can yield important benefits for researchers, by allowing the better definition of the different environmental triggers, genes, and mechanisms at play in each phenotype. Patients and clinicians can be helped by this process, as well. “Once you understand these unique phenotypes, you can talk to a patient over the phone for about five to ten minutes and often get a feel for which group they’re going to fall into, and help them in terms of deciding what the next best treatments should be.”

Grandjean — connecting toxicants in diet to neurological and immunological effects

Grandjean discussed the neurotoxic and immunotoxic effects of environmental toxicants that bioaccumulate in marine food chains and end up in seafood, especially if the diet includes marine mammals, such as the pilot whale. Grandjean showed data from prospective epidemiological studies of birth cohorts in the Faroe Islands north of Scotland. In this fishing community, his team has conducted more than 8,000 extensive clinical evaluations of cohort members.

In the first part of his talk, Grandjean described his work with environmental toxicants, such as methylmercury and the organic pollutants polychlorinated biphenyls (PCBs) and perfluorinated compounds (PFCs), in terms of their effects on development. According to him, the effects clearly depend on the nature and dose of the toxicant. Grandjean also said that there seems to be a window of vulnerability where exposure to neurotoxicants could be most detrimental to a child’s health. His group found changes in brain architecture and electrical signaling, as well as significant developmental deficits in motor function, attention, visuospatial function, language, and visual memory associated with increased methylmercury exposures.

Immunotoxicants reduce the effectiveness of immunization in children

In the second part of his talk, Grandjean explored the interaction of immunotoxicants and vaccines. His team measured PFCs in the mother’s serum during pregnancy, and later checked for the compounds in samples from the children at age five. Grandjean presented evidence to suggest that exposure to immunotoxicants is linked to a significant reduction in the effectiveness of tetanus and diphtheria immunization in triggering an antibody response, a reflection of how well the immune system is functioning.

“There are known problems with vaccine efficiency around the world,” Grandjean concluded. “We need to work together to ensure both at an individual level that we’re all protected from the diseases we’re vaccinated against and also at a population level that we keep immunity at a sufficiently high level to prevent epidemics from happening.”

(Anshul Pandya, Ph.D., is an Intramural Research Training Award fellow in the NIEHS Laboratory of Neurobiology Ion Channel Physiology Group.)




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