Jan. 14, 2005 ROCHESTER, Minn. -- A discovery by a Mayo Clinic research team may pave the way for the creation of new drugs to treat rheumatoid arthritis (RA) lung disease, which affects an estimated 500,000 patients in the United States. Currently, there are no effective treatments for RA lung disease.
In a paper that appears in today's online version of the Jan. 13 edition of Arthritis & Rheumatism, http://www3.interscience.wiley.com/cgi-bin/jtoc/76509746/, the researchers report that RA lung disease may operate much differently from other forms of lung disease. If further studies support this finding, it could change the way RA lung disease is treated as well as the design focus of drugs developed to treat it.
The Mayo Clinic research paper describes a staining method the team refined for identifying markers in RA patients' lung tissues. The results establish two key points never before fully documented in the laboratory:
* Certain specific T cells of the immune system, whose normal job in healthy people is to attack disease organisms that invade the body, are more abundant in tissue samples from patients with RA lung disease than in tissue samples from patients who have other forms of lung disease. This finding supports the concept that RA lung disease may be fundamentally different from other forms of lung disease -- and should be treated differently.
* RA lung disease detection can be improved through the technological advance of computer-assisted image analysis. This improvement allows the disease to be diagnosed early and treated aggressively as a disease of the immune system.
"Many doctors who have seen our results say, 'This is what I've always believed.' But no one had proved it to them," says Carl Turesson, M.D., Ph.D., former Mayo Clinic research fellow now working at Malmo University Hospital in Sweden. Says Dr. Turesson, "Our work provides the evidence that was lacking, so from that standpoint, it is a very helpful demonstration that hopefully will lead to the development of new treatment strategies for RA lung disease."
In the Mayo Clinic laboratories, Dr.Turesson and colleagues examined 31 lung tissue biopsy specimens. Of those, 15 were from patients previously diagnosed with RA lung disease, and 16 were from patients who, although not suffering from RA lung disease, also had a disease affecting the lung tissue, interstitial lung disease. No one on the research team knew the diagnosis of a given specimen. All specimens were stained to enhance certain T cell subtypes and then examined by digital images magnified 100 times. The staining patterns were quantified using computer-assisted image analysis. Results from the 11,412 images analyzed indicated that tissue samples from RA lung disease patients consistently showed elevated numbers of a subset of T cells known as CD4 and CD3 cells.
Practical Implications of the Research
At least two immediate implications of this research could change the way researchers are attempting to design RA lung disease drugs and how aggressively RA lung disease patients are treated. First, the abundance of CD4 and CD3 cells in RA lung disease tissue suggests therapies specifically directed against T cells and T cell function may succeed where earlier therapeutic approaches did not. Explains Dr. Turesson: "This is a rationale for trying newer approaches to treating RA lung disease that involve drugs that block T cell action. That might help us make progress against this disease." Studies are ongoing to examine other important subtypes of cells involved in RA lung disease and to discover how these are related to its cause and the damage to the joints, lungs and other tissues of the body which result.
Second, data from the researchers shows that the form of RA disease that spreads beyond joints to involve the lungs is more likely to be fatal. However, if physicians can use the Mayo Clinic method for detecting early telltale signs of RA lung disease, they can decide to treat the disease aggressively in its early stages and thus potentially prolong lives, according to Dr. Turesson.
About Rheumatoid Arthritis
Rheumatoid arthritis belongs to a class of diseases in which the immune system erroneously attacks the body. These are called "autoimmune" diseases. Because it is a systemwide disorder that can affect different parts of the body, RA can cause a variety of symptoms. It can work silently for years without symptoms, as in the early stages of both joint damage and RA lung disease. Symptoms can include joint pain, stiffness, inflammation, persistent cough, shortness of breath and fever. RA affects an estimated 1 percent of the U.S. population, about 2.1 million Americans, according to the Arthritis Foundation, http://www.arthritis.org. Of these, nearly one-half may have some abnormal lung function. Up to one-fourth -- about 500,000 Americans -- develop RA lung disease. In RA lung disease, the air sacs of the lung (alveoli) and the structures that support them become so damaged by inflammation that they become scarred, impairing effective lung functioning.
Collaboration and Support
In addition to Dr. Turesson, other Mayo Clinic investigators included: Eric Matteson, M.D.; Thomas Colby, M.D.; Zvezdana Vuk-Pavlovic, Ph.D.; Robert Vassallo, M.D.; Henry Tazelaar, M.D.; and Andrew Limper, M.D. Cornelia Weyand, M.D., Ph.D., former Mayo Clinic rheumatologists, now working at Emory University in Atlanta, also collaborated.
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