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Blood Test Predicts Lymphedema

Circulating proteins accurately ‘flag’ disorder’s presence (Dec. 18)

Researchers at the Stanford University School of Medicine have identified a set of proteins circulating in blood whose levels accurately “flag” the presence of lymphedema. The new findings, reported in PloS One, suggest that clinicians will finally be able to detect — and eventually treat — this common but relatively neglected condition, which affects an estimated 10 million people in the U.S.

Lymphedema is an often-painful inflammatory condition resulting from the blockage of lymphatic vessels, which ordinarily drain fluid from tissues throughout the body. In the developed world, lymphedema most often occurs as an unintended consequence of radiation therapy for cancer. According to senior author Stanley Rockson, MD, about one in four breast-cancer survivors eventually develops lymphedema. Numerous other factors, including parasitic infections endemic in some developing countries, can also cause the disorder, he said.

The blunting of normal immune-cell flow due to the blockage of lymphatic vessels helps to trigger the buildup of fluid within affected areas of the body. This fluid buildup, in turn, can cause thickening of the skin, severe inflammation, the accumulation of fibrous tissue, excessive blood-vessel formation, and marked expansion of the fatty layer beneath the skin.

By the time the main symptom — swelling of one or more limbs — is detectable, the condition may have gotten such a foothold that it becomes difficult or impossible to reverse, at least with current treatment options, Rockson said.

Currently, the only way to diagnose lymphedema is by physical inspection, and all too often the disorder is misdiagnosed or overlooked altogether. The biological events behind the condition may be present for 5 years or more before symptoms become evident, said Rockson. Moreover, no drugs are available for effectively treating the disorder.

For the new study, Rockson and his colleagues obtained skin biopsy samples of both lymphedematous and normal tissue from 27 patients. Using advanced molecular methods, the researchers compared each patient’s diseased tissue with his or her healthy tissue to see which genes were engaged in the generation of their respective protein products in diseased versus healthy tissue. Thousands of genes fit the bill. Then the investigators narrowed their search to the overproduced proteins themselves — in particular, to proteins that were already known to circulate throughout the bloodstream of all people, including healthy ones, and for which fast, commercial blood tests already exist.

A panel of tests that measured the levels of six different proteins in study subjects’ blood was able to distinguish the lymphedematous patients from control subjects who did not have lymphedema. None of these six proteins was predictive by itself; in aggregate, however, their presence at certain levels and ratios appeared to serve as a biological biomarker for lymphedema.

Interestingly, all six proteins are well known, and each is associated with one or more hallmark biological features of chronic lymphedema: the accumulation of fibrous deposits, the stimulation of fat-cell activity, inflammation, and lymphatic-vessel formation and repair. “These biomarkers may themselves lead us to valuable pharmaceutical targets,” Rockson remarked.

To determine the validity of their biomarker panel, Rockson and his colleagues collected blood from a new cohort of 36 lymphedematous and 15 healthy adults, extracted blood samples, and tested the samples with the panel. The test distinguished patients with lymphedema from healthy subjects with an accuracy approaching 90% — good enough for use as a clinical diagnostic tool and a vast improvement over current detection methods, Rockson said.

Source: Stanford University School of Medicine; December 18, 2012.

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