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NIH scientists develop rapid
test for Sjögren’s syndrome
By LYNN YOFFEE
Medical Device Daily Staff Writer
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.
MEDICAL DEVICE INNOVATION 2010
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.”
(This story originally appeared in the Aug. 24, 2009,
edition of Medical Device Daily)
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