The autoimmune disease known as Sjögren's syndrome can cause a wide-ranging list of ill effects from irritating to life-threatening. Current tests usually diagnose the condition only about half the time, adding to treatment complications.

Scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, are in the process of developing a rapid, automated test that correctly diagnoses the syndrome three out of four times and with strong accuracy.

"We've developed a new technology; no one else has done this. We've built a large panel of tests for autoimmune targets," Peter Burbelo, PhD, a scientist at NIDCR heading up the research, told Medical Device Daily.

Burbelo is referring to luciferase immunoprecipitation system (LIPS), which uses mammalian cell-produced recombinant antigens for analyzing Sjögren's autoantibody responses.

Currently doctors test for two antibodies that are often associated with the condition, but these blood tests tend to detect the more strongly associated antibody, called SSB. But it works only about 45% of the time.

"We found that our assay picked up 75% of SSB antibody," he said. It also identifies a second related antibody, called SSA.

Sjögren's causes the immune system to turn against the body's own cells, commonly affecting the glands that produce saliva and tears. But the disease can attack more than that, manifesting in joint inflammation, various types of autoimmune thyroid, kidney, liver, lung, and skin diseases, and changes in nerve function of the upper or lower limbs. Some people with Sjögren's are also more prone to develop lymphoma.

In addition to using current blood tests, physicians typically opt to biopsy a salivary gland to see if there's an inflammatory attack.

LIPS would avoid the need for biopsies and offer a rapid diagnosis from a reference lab. But Burbelo envisions that the test could eventually be developed for point-of-care use.

LIPS is a traditional assay in which an antigen, or segment of a protein known to elicit an antibody response, is fused to an enzyme similar to the light-producing luciferase that produces the flash in fireflies.

"The antigen binds to what I'll call the flashlight protein," he said. "We capture those antibodies. If they glow, it means you have antibodies to the target."

The greater the intensity of the light flash, the more target antibody there is bound to the antigen.

But what makes LIPS different from other assays is its sensitivity.

In his team's most recent work, reported in the current issue of Autoimmunity, Burbelo and colleagues used the test on 82 people, 57 of whom had well-characterized primary Sjögren's syndrome.

They reported that 42 of the study's 57 patients had antibody reactions against a segment of the Ro52 antigen that does not elicit a response in currently used ELISA tests, a sign of the LIPS assay's greater sensitivity, he said.

LIPS was able to detect antibody responses against each protein in about 60% of cases, equal to an ELISA, but with greater specificity. They also tested for other conditions that aren't usually linked to Sjögren's syndrome, but are anecdotally reported by patients.

"We hypothesized that if we made antigens for the thyroid, stomach and peripheral nervous system, LIPS could pick out the subset of patients with antibodies against these tissues," said Mike Iadarola, PhD, another NIDCR scientist and senior author on the study.

The researchers discovered that 14% of the patients had antibodies against the thyroid antigen, 16% had antibodies against an antigen associated with autoimmune gastritis and 4% had antibodies linked to an autoimmune attack of the eye's peripheral nerve.

Burbelo said this aspect of the test will go a long way in terms of helping physicians to diagnose the disease in patients that present with a set of symptoms that aren't commonly assumed to be a result of Sjögren's syndrome. It also opens the door to further study the disease and how it affects the entire body, beyond the salivary and tear glands.

The test will require further refinement before it's ready to commercialize.

"It's not ready for prime time in the sense that we don't have a commercial developer," he said, adding that his team is busy developing LIPS for applications in other autoimmune diseases. "We're still trying to build more tests and trying to find new biomarkers for diseases where there aren't any, like fibromyalgia."

Lynn Yoffee, 770-361-4789; lynn.yoffee@ahcmedia.com