[MOL] nancy P. This one is for you! [01328] Medicine On Line

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[MOL] nancy P. This one is for you!

Enzyme Blamed As Cause Of Lupus

Associated Press
May 31, 2000

The Associated Press

German scientists have provided the first direct evidence that a key enzyme's failure to mop up dying cells contributes to lupus, a potentially fatal immune disorder.

The study, published in the June issue of the journal Nature Genetics, involved only mice. However, researchers said the immune reactions are very similar to what occur in humans.

"These mice add strong support to the hypothesis that impairment of the normal disposal of cellular debris predisposes the development" of lupus, said Mark J. Walport of London's Imperial College.

Lupus is a disorder that causes the body's own defenses to mistakenly attack the DNA and proteins within healthy cells. Complications include arthritis, blood vessel inflammations and kidney failure.

Scientists believe lupus is rooted in many subtle genetic abnormalities. One of many suspected factors is a mutation that disrupts the body's waste disposal mechanism in cells.

A special enzyme known as DNase1 is supposed to eliminate what scientists call "garbage DNA" and other cellular leftovers by biochemically chopping them into tiny fragments for easier removal.

The researchers turned off the gene that encodes DNase1 in specially bred mice. The mice appeared healthy at birth. After six to eight months, up to 73 percent of the mice without the DNase1 gene were showing lupus symptoms.

The study was led by researchers in laboratories in Essen and Bochum, Germany.

Lupus patients often have low levels of DNase1. Laboratories already manufacture a synthetic version of DNase1 for other medical uses.

Walport and other researchers said it is not known whether supplementing the single enzyme would help lupus patients because DNase1 is only one factor in the complex disorder.

Because the illness is more common among women, other studies are exploring whether imbalances of certain hormones contribute to lupus. Environmental and workplace exposures also are suspected triggers.

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