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Finding out if you have celiac disease is not easy. Diagnosing the autoimmune disease in the United States requires two tests. First, a blood test to identify elevated levels of certain antibodies, most commonly tTG-IgA (tissue transglutaminase IgA). In the event of a positive blood test, an upper endoscopy with biopsy is done of the small intestine to identify signs of villous atrophy. A particularly challenging requirement of the test is that both tests must be performed while the patient maintains a diet with gluten. Once gluten is removed from the diet, the antibodies may not be present. A less cumbersome diagnostic method is an important step in identifying more people with celiac disease (which is estimated to be about 1% of the population in the United States).
Now, Brisbane-based Novoviah Pharmaceuticals has announced that their novel clinical platform technology for detecting and monitoring disease by measuring immune reactivity has been successfully tested in celiac disease. The Novoleukin test platform, developed specifically for clinical use, measures T cell reactivity in fresh whole blood after 24-hour in vitro stimulation with a target antigen. The proprietary technology boosts T-cell activity after blood collection, enabling accurate cytokine biomarker measurement and comparison with unstimulated controls. This can be used to monitor disease reactivity status and the effectiveness of prospective therapeutics.
The study tests the potential of the whole blood assay measuring interleukin-2 release (WBAIL-2) for detecting gluten-specific T cells to aid in celiac disease diagnosis. The findings are published in Gastroenterology in the paper, “Blood-based T Cell Diagnosis of Celiac Disease”.
The test platform’s utility and performance were demonstrated in collaboration with Walter and Eliza Hall Institute of Medical Research (WEHI) researchers who analyzed blood samples from 181 volunteers to identify the presence and assess the severity of celiac disease: 88 with celiac disease (75 on gluten free diet and 13 consuming gluten) and 93 controls (32 on gluten free diet with non-celiac gluten sensitivity, 61 healthy). In vitro IL-2 release in whole blood after gluten peptide stimulation was measured.
The results show high sensitivity (90%) and specificity (95%) in detecting celiac disease, even in patients following a strict gluten-free diet, which normally confounds traditional diagnostic methods.
The authors wrote that, “Gluten-stimulated IL-2 secretion indicates the presence of pathogenic gluten-specific CD4+ T cells and is a useful diagnostic for celiac disease. WBAIL-2 and serum IL-2 after gluten could be complementary and allow biopsy-free celiac disease diagnosis.” They added that WBAIL-2 may help diagnose and monitor other CD4+ T cell-driven diseases.
Indeed, the test detects as few as one gluten-specific T lymphocyte in one milliliter of blood or one per million CD4+ T cells. Beyond celiac disease, this level of sensitivity in a straightforward blood test is a technical achievement that may impact patient care in many fields, including the acceleration of immunotherapy and vaccine development.
The test was also predictive of patient responses during gluten challenge protocols, underscoring its utility in stratifying patients for clinical research and tailoring therapeutic strategies.
“By stimulating T cells after a blood draw, patients can avoid the need to return to gluten and the suffering that often comes with that—for the sole purpose of diagnosis,” noted Jason Tye-Din, PhD, MBBS, associate professor, head of WEHI’s Celiac Research Laboratory and a gastroenterologist at the Royal Melbourne Hospital. “That is a major step toward improving outcomes for patients.”
Robert Anderson, MBChB, PhD, co-founder of Novoviah Pharmaceuticals, current president of the International Society for the Study of Celiac Disease, and a practicing gastroenterologist, noted, “The test is designed for ease of use in the clinical setting. It can be prepared without specialist equipment and then sent for highly sensitive laboratory analysis. The protocol is simple and reproducible, enabling easy rollout across multiple sites.”
The Novoleukin test’s ability to detect disease and measure changes in immune response may impact drug development. “Non-invasively monitoring T cell reactivity opens the door to transformative clinical applications, particularly in drug development,” Anderson added. “The platform is already being used by leading biopharma partners to evaluate immune responses during celiac disease clinical trials, offering real-time insights into treatment efficacy.”
Established in 2020, Novoviah developed the Novoleukin antigen-specific T cell testing platform for clinical trials and explored its broader application in clinical care. Originally developed for multi-center clinical trials, the Novoleukin system has potential for broader clinical use. Novoviah is actively expanding the diagnostic applications of the Novoleukin platform across additional immune-mediated diseases, including viral infection, autoimmune conditions, and some cancers, aiming to bring T cell-guided insights to clinical and research settings.
