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| | | ![]() Diagnostic Technique Shows Promise for Primary Sjögren's Syndrome BETHESDA, Md -- August 19, 2009 -- For the thousands of individuals in the United States who will be evaluated this year for Sjögren's syndrome, phsycians will likely test for 2 antibodies that are often associated with the condition. The problem is today's standard blood tests detect the more strongly associated antibody, SSB, only about half the time, making the meaning of a negative result uncertain. However, a rapid, automated test that can identify the SSB antiboyd correctly 3 out of 4 times with 100% accucary is now under development. The study is published online in the journal Autoimmunity. The test, called luciferase immunoprecipitation technology (LIPS), also detected a second antibody, SSA, about as well as today's standard assays in the group's initial study of 82 people, 57 of whom had well-characterised primary Sjögren's syndrome. Peter Burbelo, PhD, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, Maryland, and colleagues also reported using LIPS to profile additional antibodies of interest that may be related to other largely unrecognised manifestations of the syndrome. Short for luciferase immunoprecipitation technology, LIPS is a traditional bait-and-bind diagnostic assay. The bait is any recombinant laboratory-made antigen, or segment of a protein known to elicit an antibody response, that is then fused to an enzyme similar to the light-producing luciferase that produces the flash in fireflies. The greater the intensity of the light flash, the more target antibody there is bound to the antigen. What makes LIPS different from other antibody tests is its extreme sensitivity, or ability to correctly detect an antibody of interest. According to Dr. Burbelo, an Enzyme-Linked ImmunoSorbent Assay (ELISA) typically has a dynamic range of between 5 and 15,000 units of signal, but with LIPS, researchers can see samples that range from zero to sometimes over a million units of signal. This zero-to-million diagnostic window allows researchers to more objectively measure any antibody response associated with an autoimmune disorder. It also suggests LIPS may have the potential to detect most developing autoimmune disorders before they become symptomatic, more closely monitor the ups and downs of a patient's antibody counts over time, and track the immunological outcome of an autoimmune treatment. "Traditionally, the SSA antigen consists of two proteins, Ro52 and Ro60, that are conjoined and anchored on the plastic diagnostic assays," said senior author Mike Iadarola, PhD, NIDCR. "We teased apart the 2proteins to present their full 3-dimensional shape and were able to measure the antibody response to each separately." The group found that 42 of the study's 57 previously diagnosed Sjögren's patients had antibody reactions against a segment of the Ro52 antigen that does not elicit a response in today's ELISA tests, a sign of the LIPS assay's greater sensitivity. Overall, LIPS detected antibody responses against each protein in about 60% of patients, roughly equal to an ELISA, but with a far greater dynamic range and perfect specificity. The scientists then decided to test for other conditions not traditionally linked to Sjögren's syndrome but that occasionally have been reported in some patients. "We hypothesised 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 Dr. Iadarola. The scientists found 14% of their Sjögren's 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. These findings suggest that LIPS may be used as a substitute for more invasive and expensive procedures typically used to diagnose these peripheral conditions. "Again, this study is just a start," said Burbelo. "All of these tests can be performed on the automated robotic machine in my laboratory, and we can do thousands a day. There's more data to come." SOURCE: National Institutes of Health
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