Latest news with #WalterandElizaHallInstitute
Sydney Morning Herald
6 days ago
- Science
- Sydney Morning Herald
The cancer drug, the faked data and the superstar scientist
On camera, Smyth looks nervous and drawn – a scientist out of water. But in recorded lectures to scientific colleagues, he looks far more assured. Dressed in black with his gelled grey hair, answering technical questions off the cuff, he is a man in command. 'He was a little bit aloof, he had a high opinion of himself. He saw himself as an upper-level person. But he was a nice-enough fellow,' said Brett*, a former colleague who spent time with Smyth outside work and, like others, requested anonymity to avoid professional repercussions. 'His arrogance comes across very quickly,' said a second. 'He had an ab-fab reputation,' said a third, who would later be charged with investigating him. 'That, more than anything else, is the biggest puzzle of all to me. He was not trying to achieve that level of reputation – he'd already achieved it. Why did he feel it was necessary to try for even higher acclaim than he'd already got?' From the outside, Smyth was a rising star, winning awards, publishing important papers, and being showered in millions of dollars of taxpayer research funding. But inside his lab, from the earliest days of his career, concerns were emerging. Selena*, who worked closely alongside Smyth during his time at Peter MacCallum Cancer Centre, said he only ever wanted to know the good news – even though science is littered with negative results. He 'did not want to hear about things that weren't working. He wanted to see finished results. He did not want to know how it was being done,' she said. 'You'd present raw data, and he'd say, 'You can just leave those points out – they are outliers'.' Other scientists sometimes could not reproduce his results. But rather than question Smyth, they often questioned themselves. 'Maybe he's got better hands than I have. Or maybe the mice are different,' said Brett*. 'There are all these variables.' In 2004, Smyth was the senior author on a paper in top journal Nature Immunology, which was such a sensation that his co-author was nominated for a National Association of Research Fellows award, where Professor David Vaux was secretary. Vaux, 65, is one of Australia's most important cancer researchers, past deputy director of the Walter and Eliza Hall Institute and winner of as many prizes as Smyth. He is also one of the very few researchers willing to take on the scientific establishment when he believes someone is committing research misconduct. A third thing to know about Vaux: when he goes to the doctor, he loves to read the Australian Women's Weekly. The puzzles where you have to spot differences between two images are his favourite. Vaux had first come across Smyth in 1995 when he was asked to comment on a paper the young researcher submitted. He came across paragraphs that seemed similar to Vaux's own work. But when the paper was published, those paragraphs had disappeared. Still, Vaux kept half an eye on the rising star. Years later, he found himself flicking through a 2004 paper Smyth had co-authored. It contained rows of flow cytometry plots of immune cells. Each dot is meant to represent a cell. 'I just looked at them, fused the images, and it was immediately clear they had been duplicated and altered,' said Vaux. The dot pattern kept repeating, as though someone had cut and pasted together the same images in a different order. Each plot contains 10,000 cells. 'The chances of two plots having the same pattern of dots would be 1 in 10 to the power of 1000.' Vaux emailed the paper's authors. 'I can clearly see the problems – one dotplot has been duplicated and modified and used for at least 6 of the plots presented in that revised figure. I still haven't been able to track Mark down,' one wrote back. 'I feel sick.' Nature Immunology launched an investigation and in 2006 retracted the paper because 'it contains a number of errors, including duplications of some flow cytometry plots'. To this day, it is not clear if it was Smyth who duplicated the plots. But a retraction is an enormous black mark on a scientist's career. Peter MacCallum Cancer Centre put in place compulsory research integrity training, including a seminar entitled 'Scientists Behaving Badly: Fraud & Misconduct'. This was only the start of Smyth's troubles. In 2014, a thin unmarked envelope was slipped under David Vaux's office door. Inside, under a cover note from 'a concerned scientist', was a copy of a secret Peter Mac investigation into Mark Smyth. The investigation started in 2012, when one of Smyth's PhD students was running a cancer experiment in mice. But the data wasn't good. It looked like another negative experiment. Then, according to the student's evidence, Smyth provided him with a new spreadsheet. It contained records of 20 mice Smyth claimed he had kept as a 'side project'. Smyth said he'd been running the same experiment – with better results. He suggested combining the data, making the results much more positive. At Peter Mac, mice were tracked closely on its Mighty Mouse database, which recorded their births, deaths and every experiment. The student could find no record of Smyth's additional mice on Mighty Mouse. He told Smyth, who suddenly advised tossing the new data. Instead, the concerned student went to Peter Mac, which launched a preliminary investigation. Smyth's personal lab book contained 'not entirely convincing' partial records for 14 of the mice, 'crowded into unlikely spaces', the preliminary investigative report, also obtained by this masthead, says. A further six mice were recorded in a book belonging to a lab assistant. But she told the inquiry she had no memory of monitoring the mice or writing the data in her lab book. She said the handwriting was not hers. 'The animal technicians are right on the ball. If they say a cage of mice, that they know Mark is talking about, never existed – it's not really possible,' one investigator told this masthead, speaking under condition of anonymity to detail confidential information. Peter Mac's preliminary investigation found no independent evidence the mice ever existed and concluded Smyth had a case to answer. 'I thought it wasn't marginal,' said the investigator. 'I thought at the time: 'This guy is in serious trouble here'.' But under an unusual arrangement, the University of Melbourne is responsible for conducting research misconduct investigations at Peter Mac. The sandstone institution would conduct the full investigation. A finding he had made up mice could end Smyth's glittering career. But Smyth's luck turned. On the day of his hearing in front of an expert panel, a Peter Mac employee produced a new datasheet. It was apparently written by Smyth and then 'mislaid'. The employee said they found it while clearing out his office. It contained an error-riddled record for the 20 mice. A handwriting expert brought in by the inquiry determined both this rediscovered loose sheet of paper and the records in the lab assistant's lab book – the ones she said she did not write – were likely written by the same person. That person may have been Smyth, the panel was told. But the expert couldn't be sure. Smyth claimed the central database that recorded mice was often faulty and not fit for purpose. Two of Smyth's colleagues told the panel they had similar problems with the database. One of those colleagues was the person who found Smyth's 'mislaid' data sheet. The other, Robert*, now says the panel misconstrued his evidence. 'When they asked me directly if the mice in question could have existed, I was very clear and responded with a 'no',' he said. 'It does haunt me that my statements have been twisted to allow Mark to escape punishment.' The panel concluded Smyth did not make up the data. He was in the clear. 'It's very hard to understand how Melbourne University could say he wasn't fabricating the data, making it up, and then six or seven years later he's done exactly the same thing at QIMR,' Robert told this masthead. 'Melbourne University needs to take some accountability for allowing Mark to continue misleading scientists and patients.' A senior Australian scientist with close knowledge of the case, speaking anonymously due to restrictions in their employment contract, is absolutely scathing. 'As they'd done with a number of integrity cases, [the University of Melbourne] … concluded there was nothing to see here,' they said. 'The institutional lens is: we have to avoid any suggestion the University of Melbourne has dodgy people, so let's find him not guilty and move him on.' University of Melbourne deputy vice chancellor Professor Mark Cassidy said in a statement that all complaints and allegations were taken seriously and addressed in line with the appropriate guidelines. GSK said its oncology research and development program was 'robust'. 'Our investigations of Nelistotug in combination with other therapies is always based on the full breadth of scientific evidence available,' it said. Smyth was hired by QIMR in 2012, before the Peter Mac allegations were made, and left to join the Queensland-based institute in 2013 - before the investigation was concluded. The allegations he faced soon became the subject of water-cooler gossip, both in Victoria and in Queensland. 'It was a pretty open secret at Peter Mac that Mark Smyth was fudging data,' said a former Peter Mac PhD student. 'No one believed it. It all looked fake.' Smyth himself has never spoken publicly about the saga, he left QIMR and this masthead was not able to confirm where he was now working. Approached recently at a house in a leafy Brisbane suburb a few minutes' drive from his former QIMR lab, he said he was 'not interested' in responding to the allegations, immediately turning down a printed list of questions as he unpacked golf clubs from his car. 'No thanks, I've been asked … a million times,' Smyth said. Asked twice if he stood by his work and research, he said: 'Can you please just get away. I'm not interested. See you later.'
The Age
6 days ago
- Science
- The Age
The cancer drug, the faked data and the superstar scientist
On camera, Smyth looks nervous and drawn – a scientist out of water. But in recorded lectures to scientific colleagues, he looks far more assured. Dressed in black with his gelled grey hair, answering technical questions off the cuff, he is a man in command. 'He was a little bit aloof, he had a high opinion of himself. He saw himself as an upper-level person. But he was a nice-enough fellow,' said Brett*, a former colleague who spent time with Smyth outside work and, like others, requested anonymity to avoid professional repercussions. 'His arrogance comes across very quickly,' said a second. 'He had an ab-fab reputation,' said a third, who would later be charged with investigating him. 'That, more than anything else, is the biggest puzzle of all to me. He was not trying to achieve that level of reputation – he'd already achieved it. Why did he feel it was necessary to try for even higher acclaim than he'd already got?' From the outside, Smyth was a rising star, winning awards, publishing important papers, and being showered in millions of dollars of taxpayer research funding. But inside his lab, from the earliest days of his career, concerns were emerging. Selena*, who worked closely alongside Smyth during his time at Peter MacCallum Cancer Centre, said he only ever wanted to know the good news – even though science is littered with negative results. He 'did not want to hear about things that weren't working. He wanted to see finished results. He did not want to know how it was being done,' she said. 'You'd present raw data, and he'd say, 'You can just leave those points out – they are outliers'.' Other scientists sometimes could not reproduce his results. But rather than question Smyth, they often questioned themselves. 'Maybe he's got better hands than I have. Or maybe the mice are different,' said Brett*. 'There are all these variables.' In 2004, Smyth was the senior author on a paper in top journal Nature Immunology, which was such a sensation that his co-author was nominated for a National Association of Research Fellows award, where Professor David Vaux was secretary. Vaux, 65, is one of Australia's most important cancer researchers, past deputy director of the Walter and Eliza Hall Institute and winner of as many prizes as Smyth. He is also one of the very few researchers willing to take on the scientific establishment when he believes someone is committing research misconduct. A third thing to know about Vaux: when he goes to the doctor, he loves to read the Australian Women's Weekly. The puzzles where you have to spot differences between two images are his favourite. Vaux had first come across Smyth in 1995 when he was asked to comment on a paper the young researcher submitted. He came across paragraphs that seemed similar to Vaux's own work. But when the paper was published, those paragraphs had disappeared. Still, Vaux kept half an eye on the rising star. Years later, he found himself flicking through a 2004 paper Smyth had co-authored. It contained rows of flow cytometry plots of immune cells. Each dot is meant to represent a cell. 'I just looked at them, fused the images, and it was immediately clear they had been duplicated and altered,' said Vaux. The dot pattern kept repeating, as though someone had cut and pasted together the same images in a different order. Each plot contains 10,000 cells. 'The chances of two plots having the same pattern of dots would be 1 in 10 to the power of 1000.' Vaux emailed the paper's authors. 'I can clearly see the problems – one dotplot has been duplicated and modified and used for at least 6 of the plots presented in that revised figure. I still haven't been able to track Mark down,' one wrote back. 'I feel sick.' Nature Immunology launched an investigation and in 2006 retracted the paper because 'it contains a number of errors, including duplications of some flow cytometry plots'. To this day, it is not clear if it was Smyth who duplicated the plots. But a retraction is an enormous black mark on a scientist's career. Peter MacCallum Cancer Centre put in place compulsory research integrity training, including a seminar entitled 'Scientists Behaving Badly: Fraud & Misconduct'. This was only the start of Smyth's troubles. In 2014, a thin unmarked envelope was slipped under David Vaux's office door. Inside, under a cover note from 'a concerned scientist', was a copy of a secret Peter Mac investigation into Mark Smyth. The investigation started in 2012, when one of Smyth's PhD students was running a cancer experiment in mice. But the data wasn't good. It looked like another negative experiment. Then, according to the student's evidence, Smyth provided him with a new spreadsheet. It contained records of 20 mice Smyth claimed he had kept as a 'side project'. Smyth said he'd been running the same experiment – with better results. He suggested combining the data, making the results much more positive. At Peter Mac, mice were tracked closely on its Mighty Mouse database, which recorded their births, deaths and every experiment. The student could find no record of Smyth's additional mice on Mighty Mouse. He told Smyth, who suddenly advised tossing the new data. Instead, the concerned student went to Peter Mac, which launched a preliminary investigation. Smyth's personal lab book contained 'not entirely convincing' partial records for 14 of the mice, 'crowded into unlikely spaces', the preliminary investigative report, also obtained by this masthead, says. A further six mice were recorded in a book belonging to a lab assistant. But she told the inquiry she had no memory of monitoring the mice or writing the data in her lab book. She said the handwriting was not hers. 'The animal technicians are right on the ball. If they say a cage of mice, that they know Mark is talking about, never existed – it's not really possible,' one investigator told this masthead, speaking under condition of anonymity to detail confidential information. Peter Mac's preliminary investigation found no independent evidence the mice ever existed and concluded Smyth had a case to answer. 'I thought it wasn't marginal,' said the investigator. 'I thought at the time: 'This guy is in serious trouble here'.' But under an unusual arrangement, the University of Melbourne is responsible for conducting research misconduct investigations at Peter Mac. The sandstone institution would conduct the full investigation. A finding he had made up mice could end Smyth's glittering career. But Smyth's luck turned. On the day of his hearing in front of an expert panel, a Peter Mac employee produced a new datasheet. It was apparently written by Smyth and then 'mislaid'. The employee said they found it while clearing out his office. It contained an error-riddled record for the 20 mice. A handwriting expert brought in by the inquiry determined both this rediscovered loose sheet of paper and the records in the lab assistant's lab book – the ones she said she did not write – were likely written by the same person. That person may have been Smyth, the panel was told. But the expert couldn't be sure. Smyth claimed the central database that recorded mice was often faulty and not fit for purpose. Two of Smyth's colleagues told the panel they had similar problems with the database. One of those colleagues was the person who found Smyth's 'mislaid' data sheet. The other, Robert*, now says the panel misconstrued his evidence. 'When they asked me directly if the mice in question could have existed, I was very clear and responded with a 'no',' he said. 'It does haunt me that my statements have been twisted to allow Mark to escape punishment.' The panel concluded Smyth did not make up the data. He was in the clear. 'It's very hard to understand how Melbourne University could say he wasn't fabricating the data, making it up, and then six or seven years later he's done exactly the same thing at QIMR,' Robert told this masthead. 'Melbourne University needs to take some accountability for allowing Mark to continue misleading scientists and patients.' A senior Australian scientist with close knowledge of the case, speaking anonymously due to restrictions in their employment contract, is absolutely scathing. 'As they'd done with a number of integrity cases, [the University of Melbourne] … concluded there was nothing to see here,' they said. 'The institutional lens is: we have to avoid any suggestion the University of Melbourne has dodgy people, so let's find him not guilty and move him on.' University of Melbourne deputy vice chancellor Professor Mark Cassidy said in a statement that all complaints and allegations were taken seriously and addressed in line with the appropriate guidelines. GSK said its oncology research and development program was 'robust'. 'Our investigations of Nelistotug in combination with other therapies is always based on the full breadth of scientific evidence available,' it said. Smyth was hired by QIMR in 2012, before the Peter Mac allegations were made, and left to join the Queensland-based institute in 2013 - before the investigation was concluded. The allegations he faced soon became the subject of water-cooler gossip, both in Victoria and in Queensland. 'It was a pretty open secret at Peter Mac that Mark Smyth was fudging data,' said a former Peter Mac PhD student. 'No one believed it. It all looked fake.' Smyth himself has never spoken publicly about the saga, he left QIMR and this masthead was not able to confirm where he was now working. Approached recently at a house in a leafy Brisbane suburb a few minutes' drive from his former QIMR lab, he said he was 'not interested' in responding to the allegations, immediately turning down a printed list of questions as he unpacked golf clubs from his car. 'No thanks, I've been asked … a million times,' Smyth said. Asked twice if he stood by his work and research, he said: 'Can you please just get away. I'm not interested. See you later.'
The Star
26-06-2025
- Health
- The Star
No more getting sick to diagnose coeliac disease
Coeliac disease requires patients to completely avoid foods containing gluten, while a gluten intolerance usually allows some leeway. – dpa Diagnosing coeliac disease has long been an arduous and daunting process in which people thought to have the condition have to eat wheat – the very food that will make them sick if the concerns prove true. But a new 'game changer' method could make running the gluten gauntlet a thing of the past, according to developers at Australia's Walter and Eliza Hall Institute (WEHI) in Victoria and Brisbane-based Novoviah Pharmaceuticals. They claim their 'world-first' blood test can diagnose the disease even among people who switch to gluten-free diets as a precaution. Published in the medical journal Gastroenterology , the team's work details how 'gluten-specific T-cells can detect coeliac disease, even when no gluten has been eaten'. Not only could the new test pinpoint who could be 'at risk of severe reactions to gluten', it raises the prospect of preemptive detection of 'silent' disease among those who are asymptomatic. Around 80% of potential cases worldwide could be going undiagnosed, according to the researchers, who pointed out that 'many people are deterred from seeking a definite diagnosis because they do not want to consume gluten and be sick'. 'This new test promises to simplify and speed up accurate diagnosis, while also avoiding the suffering that comes with eating gluten for extended periods to reactivate coeliac disease,' said WEHI consultant gastroenterologist Associate Professor Dr Jason Tye-Din. 'This breakthrough is deeply personal as it could spare others from the gruelling diagnostic process I had to endure,' said WEHI PhD student Olivia Moscatelli, a member of the research team who was confirmed to have coeliac disease when she was 18. An immune reaction to the gluten protein found in wheat, rye and barley, coeliac disease damages the intestine and prevents sufferers from absorbing nutrients, with some estimates suggesting that it could affect one in 100 people worldwide. – dpa
Business Wire
23-06-2025
- Business
- Business Wire
Forte Biosciences Announces Positive Data in FB102 Celiac Disease Phase 1B Study
DALLAS--(BUSINESS WIRE)--Forte Biosciences, Inc. ( (NASDAQ: FBRX), a clinical-stage biopharmaceutical company focused on autoimmune and autoimmune-related diseases, today announced positive data from a Phase 1b trial in celiac disease for lead program FB102 (FB102-101). The company will be hosting a conference call today at 8:30 am ET. Prof. Jason Tye-Din, Head of Celiac Research at the Walter and Eliza Hall Institute and principal investigator in the FB102-101 study will be participating in the call. Please connect to the call using the following link: The event and accompanying slides can also be accessed by visiting the investor relations section of the company's website at An archived webcast will be available on the company's website following the event. The FB102-101 Phase 1b celiac disease study enrolled 32 subjects 3:1 randomized (24 on FB102 and 8 on placebo). Subjects received 4 doses of FB102 (10 mg/kg) and underwent a 16 day gluten challenge. In addition to safety and tolerability, the study assessed morphologic and inflammatory endpoints along with gluten challenge (GC) induced symptoms. FB102 demonstrated a statistically significant benefit on the composite histological VCIEL endpoint (change from baseline). The mean VCIEL change from baseline was -1.849 for placebo subjects compared to 0.079 for FB102 treated subjects (p=0.0099). The change in the density of CD3-positive T cells, or IELs, from baseline was an increase of 13.3 for placebo subjects compared to a decline of 1.5 for FB102 treated subjects (p=0.0035). Baseline IEL density was 25.6 for the placebo subjects and 23.5 for the FB102 treated subjects. The mean change in the Vh:Cd ratio from baseline was -0.173 (0.21) for placebo subjects compared to -0.046 (0.09), a 73% improvement for FB102 treated subjects compared to placebo. Gluten challenge induced GI symptoms (nausea, vomiting, diarrhea, abdominal pain and abdominal bloating) reported during the 16 day gluten challenge from patient diaries/AE collection demonstrated a 42% benefit for FB102 treated subject (4.0 events per subject) compared to placebo (6.9 events per subject). There were no dropouts in the study. Treatment emergent adverse events (TEAE) were primarily mild (grade 1) with no grade 3 or higher SAEs reported in the FB102 arm. 'We want to congratulate all of the investigators and researchers that supported this study. I also want to acknowledge the incredible dedication and hard work of the Forte team. Celiac disease is debilitating for many patients with even trace exposure to gluten. FB102 has taken a big step forward towards addressing this very large unmet need with the results from this study. The Phase 2 celiac disease study is initiating with a topline readout expected in 2026.' said Paul Wagner, Ph.D. CEO and Chairperson of Forte Biosciences. 'These results are also very encouraging given the biology of the additional FB102 indications including vitiligo, alopecia areata and type 1 diabetes. We also look forward to reading out the topline results of the FB102 vitiligo study in the first half of 2026.' About Forte Forte Biosciences, Inc. is a clinical-stage biopharmaceutical company that is advancing FB102, which is a proprietary anti-CD122 monoclonal antibody therapeutic candidate with potentially broad autoimmune and autoimmune-related indications. Forward-Looking Statements Forte cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as 'may,' 'will,' 'should,' 'expect,' 'plan,' 'anticipate,' 'could,' 'intend,' 'target,' 'project,' 'contemplates,' 'believes,' 'estimates,' 'predicts,' 'potential' or 'continue' or the negatives of these terms or other similar expressions. These statements are based on the Forte's current beliefs and expectations. Forward-looking statements include statements regarding Forte's beliefs, goals, intentions and expectations regarding its product candidate, FB102 and the therapeutic and commercial market potential of FB102, the expected timeline for the Phase 2 celiac study and related readout, and the expected timing of topline results for the FB102 vitiligo study. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: risks related to Forte's ability to obtain sufficient additional capital to continue to advance Forte's product candidate, FB102; uncertainties associated with the clinical development and regulatory approval of Forte's product candidate, FB102, including potential delays in the commencement, enrollment and completion of clinical trials; the risk that results from preclinical and the Phase 1b trials may not be predictive of future results from clinical trials; risks associated with the failure to realize any value from FB102 in light of inherent risks, expense and difficulties involved in successfully bringing product candidates to market; and additional risks, uncertainties, and other information affecting Forte's business and operating results is contained in Forte's Quarterly Report on Forms 10-Q filed on May 15, 2025, and in its other filings with the Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Forte undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Source: Forte Biosciences, Inc.
Medscape
17-06-2025
- Health
- Medscape
Celiac Blood Test Eliminates Need for Eating Gluten
Think your patient may have celiac disease? The harsh reality is that current diagnostic tests require patients to consume gluten for an accurate diagnosis, which poses challenges for individuals already avoiding gluten. A more tolerable approach appears to be on the horizon. Researchers in Australia have developed a blood test that can identify celiac disease with high sensitivity and specificity, even without consuming gluten. 'This is a simple and accurate test that can provide a diagnosis within a very short time frame, without the need for patients to continue eating gluten and feeling sick, or to wait months for a gastroscopy,' Olivia Moscatelli, PhD candidate, Tye-Din Lab, Walter and Eliza Hall Institute and University of Melbourne, Parkville, Australia, told Medscape Medical News . The study was published online on June 9 in Gastroenterology . Most Cases Go Undiagnosed Celiac disease is an autoimmune disorder triggered by gluten found in wheat, rye, and barley. The only available treatment is a strict, life-long gluten-free diet. The global prevalence of celiac disease is estimated at around 1%-2%, with 50%-80% of cases either undiagnosed or diagnosed late. That's because the current reliable diagnosis of celiac disease requires the intake of gluten, which may deter people from seeking a diagnosis. In earlier work, the researchers, working with Robert Anderson, MBChB, BMedSc, PhD, now with Novoviah Pharmaceuticals, made the unexpected discovery that interleukin-2 (IL-2) spiked in the blood of people with celiac disease shortly after they ate gluten. But would this signal be present when no gluten had been consumed? The team developed and tested a simple whole blood assay measuring IL-2 release (WBAIL- 2) for detecting gluten-specific T cells to aid in diagnosing celiac disease. They collected blood samples from 181 volunteers — 75 with treated celiac disease on a gluten-free diet, 13 with active untreated celiac disease, 32 with nonceliac gluten sensitivity and 61 healthy controls. The blood samples were mixed with gluten in a test tube for a day to see if the IL-2 signal appeared. The WBAIL-2 assay demonstrated high accuracy for celiac disease, even in patients following a strict gluten-free diet. For patients with HLA-DQ2.5+ genetics, sensitivity was 90% and specificity was 95%, with lower sensitivity (56%) for patients with HLA-DQ8+ celiac disease. The WBAIL-2 assay correlated strongly with the frequency of tetramer-positive gluten-specific CD4+ T cells used to diagnose celiac disease and monitor treatment effectiveness, and with serum IL-2 levels after gluten challenge. The strength of the IL-2 signal correlated with the severity of a patient's symptoms, 'allowing us to predict how severely a person with celiac disease might react to gluten, without them actually having to eat it,' Moscatelli said in a news release. 'Current diagnostic practice involves a blood-based serology test followed by a confirmatory gastroscopy if positive. Both tests require the patient to eat gluten daily for 6-12 weeks prior for accurate results. We envision the new blood test (IL-2 whole blood assay) will replace the invasive gastroscopy as the confirmatory test following positive serology,' Moscatelli told Medscape Medical News . 'In people already following a gluten-free diet, we propose they would have this new blood test done on two separate occasions and two positive results would be required for a celiac diagnosis. This would allow a large number of people who previously have been unable to go through the current diagnostic process to receive a diagnosis,' Moscatelli said. Practice Changing Potential Blood-based test that can accurately detect celiac disease without the need for a gluten challenge would be 'welcome and practice changing,' said Christopher Cao, director, Celiac Disease Program, Division of Gastroenterology, Mount Sinai Health System, New York City. 'A typical 'gluten challenge' involves eating the equivalent of 1-2 slices of bread daily for the course of 6 weeks, and this may be incredibly difficult for patients who have already been on a gluten-free diet prior to an official celiac disease diagnosis. Inability to perform a gluten challenge limits the ability to make an accurate celiac disease diagnosis,' Cao told Medscape Medical News. 'This study shows that gluten-stimulated interleukin release 2 assays may correlate with the presence of pathogenic gluten-specific CD4+ T cell response in celiac disease,' Cao noted. He cautioned that 'further large cohort, multicenter prospective studies are needed to assess generalizability and may be helpful in evaluating the accuracy of WBAIL-2 in non-HLA DQ2.5 genotypes.' Other considerations prior to implementation may include reproducibility across different laboratories and overall cost effectiveness, Cao said. 'Ultimately in clinic, the role of WBAIL-2 will need to be better defined within the algorithm of celiac disease testing,' he added. The Path Ahead The researchers plan to test the performance of the IL-2 whole blood assay in a pediatric cohort, as well as in other countries to demonstrate the reproducibility of the test. In these studies, the test will likely be performed alongside the current diagnostic tests (serology and gastroscopy), Moscatelli told Medscape Medical News . 'There are some validation studies starting in other countries already as many celiac clinicians globally are interested in bringing this test to their clinical practice. I believe the plan is to have this as an approved diagnostic test for celiac disease worldwide,' she said. Novoviah Pharmaceuticals is managing the commercialization of the test, and the plan is to get it into clinical practice in the next 2 years, Moscatelli said.
