Study details accuracy of test in diagnosis and monitoring of celiac disease
By Amy Ratner, Medical and Science News Analyst
When a blood test measures several antibodies, the likelihood it will be accurate in confirming celiac disease increases, according to a new study done using the imaware™ test.
The study also showed that imaware™ at-home testing can be used to monitor how well the gluten-free diet is working for those who have celiac disease by tracking these same four antibodies, researchers concluded.
Published in the journal Clinical Chemistry and Laboratory Medicine, the study compared imaware™ measurement of four celiac disease antibodies in serum and plasma to conventional single antibody enzyme-linked immunosorbent assays (ELISA).
Imaware™, in one test, measures anti-tissue transglutaminase (tTG), both IgA and IgG, and deamidated gliadin peptide (DGP), both IgA and IgG. Quantitative results from the celiac disease tests used in imaware™ are aggregated and likelihood ratios are applied to determine the probability that you have celiac disease. Risk factors, including family history of celiac disease, are also taken into consideration.
Immunoglobulin A: IgA antibodies are found in the mucous membranes of the lungs, sinuses, stomach, and intestines.
Immunoglobulin G: IgG is the most common type of antibody in blood and other body fluids and protects against infection
“The study does two things. It confirms that when we test blood with imaware™, we can very accurately identify the presence of celiac disease and the absence of celiac disease,” said Jani Tuomi, a study author and imaware™ co-founder. “The test is as precise, reliable and clinically valuable as the test a doctor can do in the office.”
Secondly, the study shows drawing blood from a finger is as accurate and informative as drawing blood from a vein, he said.
Microdrop Health launched imaware™ in December as the first at-home test for celiac disease in the United States. Consumers use the test, available online for $99, to collect several drops of blood from a finger prick. They then send the sample to a Microdrop laboratory for analysis and receive results via email that links to a password-authenticated online portal.
The results of the test are not definitive for celiac disease, and consumers are advised to consult with their physician for review and the biopsy that in the United States is considered necessary for a celiac disease diagnosis.
Although the National Institutes of Health (NIH) recommend that a panel of celiac disease tests be done as part of diagnosis, physicians sometimes only test for tTG IgA. Testing is done on a larger amount of blood drawn from a vein.
Meanwhile, the Agency for Healthcare Research and Quality in 2016 concluded that tTG IgA results in accurate positive and negative results.
TTG IgA is the single blood test preferred by the American College of Gastroenterology for the detection of celiac disease in patients two years of age and older, the healthcare research agency said, noting that other tests might be needed for those who are IgA deficient. While celiac disease experts agreed with the conclusion, some pointed out that the test has some limitations.
“The ability of imaware™ to test multiple biomarkers increases the reliability, precision, and accuracy in both celiac disease screening and monitoring scenarios when compared to single biomarker tests,” Tuomi said, noting imaware™ is the first direct-to-consumer celiac disease test to be the subject of a peer-reviewed study of its effectiveness. He said the study provides the transparency about accuracy that is the missing piece in at-home testing.
The study was done by Tuomi, Detlef Schuppan, M.D., of Harvard Medical School and Johannes-Gutenberg University and Stefano Guandalini, M.D., of the University of Chicago Celiac Disease Center, researchers from SQI Diagnostics, the company that developed Microdrop’s testing equipment. Schuppan and Guandalini, recognized celiac disease experts, are scientific advisors to Microdrop.
Beyond Celiac is partnering with imaware™ to bring awareness to their home-based celiac disease test and to increase celiac disease awareness and diagnosis rates.
Researchers tested 224 blood samples. Included were 83 samples from Massachusetts General Hospital for Children and the Celiac Center at Beth Israel Deaconess Medical Center from patients who had had celiac disease confirmed by biopsy. Another 60 samples from a commercial serum banking program were from those who had positive antibody results, but no biopsy. Twenty samples were from those who had a wheat allergy and 61 who had normal blood test results. An additional 34 samples from those who had positive blood samples but no biopsy, five who had wheat allergy and 10 with normal results were also included.
Researchers used imaware™ to test the blood samples and ran numerous comparisons based on antibodies, how the blood was drawn and whether the serum or plasma component was used. Samples from Mass General and Beth Israel came from both those who were diagnosed with a biopsy and had not yet started the gluten-free diet and those who were on the diet following their diagnoses. Across all types of analysis for screening and monitoring, the accuracy of the test is greater than 90 percent, the study found.
Sensitivity and specificity are two standards by which the accuracy of testing is measured. The study found the following sensitivity and specificity for the antibodies tested: tTG IgA, 96 percent and 98 percent; tTG IgG, 89 percent and 98 percent; DGP IgA, 82 percent and 93 percent and DGP IgG, 83 percent and 90 percent.
Sensitivity – The ability of a test to correctly classify a person as having a disease
Specificity – The ability of a test to correctly classify a person as not having a disease
When imaware™ results were compared to antibody testing using ELISA, the study found that overall, tTG IgA had 99 percent agreement in results, tTG IgG, 90 percent, DGP IgA, 93 percent and DGP IgG, 90 percent. Tuomi noted that imaware™ results are based on a compilation of all four markers.
ELISA – a test that detects and measures antibodies in your blood as a way to determine if an immune response is occurring.
In an analysis of the post-test probability of confirming celiac disease, the study found that when all four types of antibodies were tested, the accuracy of the results increased to 100 percent. The analysis showed that post-test probability went up each time an additional antibody was added to celiac disease testing.
Post-test probability: the proportion of patients testing positive who truly have a disease
The results suggest that patients should always ask for more than one antibody test, despite the reliability of the tTG IgA test typically used, Tuomi said. “These are the tests you should be asking for and this is the type of result you should expect,” he said. “We would love it if you use imaware™, but even if you don’t, you should expect to get these tests.”
A comparison of blood samples drawn from a vein to the blood drawn from a finger prick found 100 percent agreement for the four antibodies. Imaware™ customers sometimes ask how the small amount of blood collected for the test compares to the larger amount collected by a physician, according to Tuomi.
The study looked at a variety of comparisons because imaware™ is used both as part of the diagnosis process and for disease management through antibody measurement. Blood samples from those who did not have biopsy confirmation would parallel those from consumers who use the test to find out if they have antibody levels that would lead to a biopsy, while samples from those who have a biopsy confirmation would align with consumers using the test for monitoring.
The study found that the test can accurately monitor response to the gluten-free diet. Higher tTG and DGP antibodies were found 94 percent of the time in celiac disease not being treated with the diet compared to 64 percent when the gluten-free diet was being followed. Tuomi attributed the relatively high percentage of positive antibodies from those on the diet to inadvertent gluten, presumably through cross-contact.
“We came to conclude that the levels of cross-contact in people who are on the gluten-free diet was more than 50 percent, so a majority of people are still being cross-contaminated. It does not take a lot [of gluten] for biomarkers to be elevated, but they can be captured and measured,” he said, noting that the percentage of those with celiac disease exposed to gluten argues for better follow-up and monitoring of celiac disease. “If you are not getting your [antibody] markers down to normal, that means you are having an immune response to elevated levels and celiac disease is wreaking damage.”
“The imaware™ at-home screening test for celiac disease is the first to combine four biomarkers in one test and provide results within several days that patients can the share with their doctors,” said Guandalini, noting that the validity of the test is supported by the data in the study. “This should help reduce the significat number of undiagnosed patients with celiac disease.”
You can read the study here.