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Piecing it Together
NIEHS Group Focuses on Puzzle of Autoimmune Diseases

By Colleen Chandler

Just behind heart disease and cancer, immune-mediated diseases are the third most common group of diseases in the United States today. Although they are becoming more and more prevalent, they are still mysterious to much of the medical community as well as the public.

Unlike heart disease and cancer, this group of diseases has not had much scrutiny and has not generated the same level of funding or interest among members of the scientific community.

Immune-mediated diseases encompass several hundred acquired disorders characterized by immune responses that cause pathology. The diseases are highly under-diagnosed and treatment is often substandard, said Dr. Fred Miller, director of the environmental autoimmunity group, or EAG, which is NIEHS' first clinical research program at the Clinical Center.

Miller is obviously not one to shy away from a challenge. Even as a young doctor, he was intrigued by the complexity of autoimmune diseases. For nearly two decades he has been piecing together this complex puzzle. He and a core group of researchers have learned much about this perplexing group of disorders, but their hypotheses have generated a lot more questions in a field already riddled with them.

The EAG will apply a multi-dimensional approach to the old problems associated with systemic autoimmune disease.

Collecting Pieces of the Puzzle – NIEHS has established the environmental autoimmunity group at the Clinical Center to begin piecing together the existing evidence and collecting new pieces of the puzzle. Members include (front, from l) Laura James Newton, Kakali Sarkar, Mehmooda Maeem, Lisa Rider and Tina Sanghvi. At rear are (from l) Adam Schiffenbauer, Bhanu Koneru, Fred Miller, Ejaz Shamim, Mark Gouley, Terry O'Hanlon and Rohanda Atkinson.

Miller said maintaining national and international networks of collaborators optimizes use of existing clinical databases and other resources, and could prompt development and validation of more accurate environmental exposure assessment tools.

The EAG already has one study under way that focuses on childhood-onset myositis. Myositis is a chronic, incurable and potentially fatal disease that strikes adults and children, incapacitating them with muscle inflammation and weakness. There are an estimated 30,000 cases in the U.S. The average myositis patient has seen seven doctors before he or she is diagnosed, Miller said. The EAG is collaborating with NIDCR on a study that will examine the composition of calcium deposits in the skin of childhood myositis patients. In another study, the group is collaborating with NIAMS to study new biologic therapies in adult myositis.

The EAG lab facilities in Bldg. 9 include sequestered environments for pre- and post-polymerase chain reaction testing to avoid contamination, a tissue-culture facility that includes a quantitative fluorescent microscope and a digital molecular imaging station.

Dr. Fred Miller

Among the challenges Miller plans for the group is identifying individual elemental disorders that are commonly lumped together as a single autoimmune disease. Miller believes there are many such syndromes, and he says lumping them all together is like comparing apples and oranges.

He intends to begin separating the apples from the oranges. A proposed study in the early stages of review will recruit people with rheumatic disorders as well as a twin or other sibling who does not have disease in an attempt to understand why one developed disease and the other did not.

"We're just getting started on what will prove to be a long but exciting journey with many surprises along the way," Miller said.

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