Refresher Course: Double Strand DNA

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Diagnosing Lupus usually involves testing positive in two tests among other

criteria. These two tests are:

ANA - Antinuclear antibodies are present in many rheumatic diseases,

and often are not specific for any single disease. They are present in

over 95% of SLE patients, 86% of scleroderma patients, and in lower frequencies

in rheumatoid arthritis (RA), Sjogren's syndrome, and polymyositis.

dsDNA - Anti-double strand DNA at a titer of 1:10 or more strongly

suggests SLE.

A U-M researcher has discovered that antibodies produced by individuals

with the autoimmune disorder systemic lupus erythematosus (SLE) actually

change the shape of the patients’ DNA molecules to produce a tighter bond

between antibodies and DNA.

Binding between lupus antibodies and DNA molecules is the first step

in a series of immunological reactions that can cause serious tissue damage

and sometimes death in lupus patients, according to D. Glick, assistant

professor of chemistry.

Glick’s discovery is significant because it is the only known example

of DNA being physically changed by an antibody and because it may lead

to the development of new drugs that can block the binding process and

prevent lupus-related tissue damage.

“Some individuals with lupus produce a unique type of antibody that

sees DNA as the ‘enemy,’” Glick explained. A component of all living organisms,

DNA is a complex molecule containing the genetic code that determines every

cell’s structure and function.

“Lupus symptoms range from mild to life-threatening, and the disease

can attack any organ in the body,” said A. Fox, chief of rheumatology

in the Department of Internal Medicine and director of the U-M Multipurpose

Arthritis and Musculoskeletal Diseases Center. “In severe cases, these

abnormal antibodies bind to sections of DNA and become lodged in the patient’s

kidneys where they trigger inflammatory reactions by white blood cells

that can lead to kidney failure.”

In future research, Glick hopes to identify the exact structural element

or feature of DNA that is targeted by lupus antibodies, and generate a

three-dimensional image of the binding site itself.

“Once we know precisely what and where the binding site is, organic

chemists may be able to synthesize a new drug that can block anti-DNA antibodies,”

Glick said. “It’s not a cure for lupus, but it could be the beginning of

an effective new treatment for the disease.”