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One Step Closer to Unlocking Lupus Mystery

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When cells in the body die, they break down into DNA, protein, and other debris, which needs to be cleared away in order for systems to function properly. The substance responsible for clearing away "cellular trash" is known as Dnase1, and German scientists have shown the first direct evidence that a deficiency in Dnase1 functioning may be one of the causes of lupus. This is because the "cellular trash" may cause the body to mount an immune response to it and to begin attacking its own cells.

The researchers found that Dnase1 levels were lower in people with lupus and in animal experiments, stopping the production of Dnase1 resulted in lupus-like symptoms.

But whether the lack of Dnase1 actually leads to disease, or simply makes the disease worse for those who already have it, is difficult for experts to agree upon.

It also is unknown what causes people to lack Dnase1. Several possibilities are under investigation, says study author Tarik Möröy, PhD, a professor of cell biology at the Institut für Zellbiologie in Essen, Germany. "There may be a loss of the Dnase1 gene" which sparks production of the enzyme, he says. "Or we may inherit a Dnase1 gene that is less effective in producing the enzyme. Environmental factors that inhibit Dnase1 activity in the [blood] is also a possibility."

The researchers also examined blood samples of 10 patients with kidney disease. Four of them had lupus, and tests showed significantly decreased Dnase1 levels.

Whether or not treating lupus patients with Dnase1 will be effective still remains to be seen. Animal experiments have shown good results, but the outcome was less optimistic with actual lupus patients. The form of Dnase1 available leaves the body almost immediately, which makes it less effective for treatment.

Möröy feels that Dnase1 might have a better effect if used early on in the disease or to prevent it rather than in patients with full-blown lupus.

But the study evidence is not definitive, and even if the scientists are correct, lupus is too complex a disease to have just one cause. "It's right now still in the stage of hypothesis and conjecture, which is based on suggestive evidence but I wouldn't go so far as to say its proven yet," Stohl says.

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