Gluten has become a major concern in American food culture over the past two decades. Much of that awareness stems from celiac disease, a condition that affects roughly 1% of the U.S. population yet remains significantly underdiagnosed. An estimated 80% of cases are either undiagnosed or caught only after years of symptoms. Part of the problem lies in how celiac has traditionally been diagnosed: patients must be actively eating gluten for blood tests and biopsies to show the characteristic intestinal damage. This requirement creates particular challenges for people who have already stopped eating gluten and begun feeling better. Recent developments in testing methods and diagnostic guidelines are beginning to address these obstacles.

What Is Celiac Disease and How Is it Diagnosed?

Celiac disease is an autoimmune condition triggered by gluten, a protein found in wheat, barley, and rye. When someone with celiac disease consumes gluten, their immune system mistakenly attacks the lining of the small intestine, damaging the tiny finger-like projections called villi that normally absorb nutrients. This damage can lead to a wide range of symptoms including digestive problems, chronic fatigue, anemia, skin rashes, and neurological issues. The severity and type of symptoms vary considerably from person to person, which is part of why the condition often goes unrecognized.

The standard diagnostic process for celiac disease in adults involves two steps. The first step involves checking for an immune system reaction to gluten through a tissue transglutaminase antibody (tTG-IgA) test. If such blood tests suggest celiac disease, the next step is an upper endoscopy with biopsy of the small intestine. During this procedure, a gastroenterologist removes small tissue samples from the duodenum to examine under a microscope. The biopsy confirms celiac disease by showing characteristic damage to the intestinal villi; this usually means they appear flattened rather than healthy and finger-like.

The “Gluten Challenge” Problem and a New Solution

Both blood tests and biopsies only work reliably when the patient is actively consuming gluten. If someone has already eliminated gluten from their diet, their intestines often begin healing and antibody levels drop, leading to false-negative results. This means patients who have stopped eating gluten must typically resume consuming it for six to eight weeks before testing, allowing enough time for antibodies to reappear and intestinal damage to develop. This requirement, known as a “gluten challenge,” creates the core difficulty of celiac diagnosis today.

The gluten challenge typically requires consuming the equivalent of four slices of bread daily, which would be enough to trigger an immune response and the intestinal damage that tests are designed to detect. This means deliberately bringing back weeks of digestive problems, fatigue, brain fog, and whatever other symptoms the patient had worked to eliminate. Many people who suspect celiac disease choose to avoid formal testing entirely rather than endure this process. Without an official diagnosis, however, they miss out on medical follow-up, insurance coverage for nutritional counseling, and the certainty that comes with knowing exactly what they’re dealing with.

Recent research has produced a potential solution to this diagnostic dilemma. Studies published in 2025 demonstrated that a new blood test called the IL-2 assay could detect celiac disease with approximately 90% sensitivity and 97% specificity, even in patients who had been following a strict gluten-free diet. The test works by exposing a patient’s blood sample to gluten in a laboratory rather than requiring the patient to consume it. When blood cells from someone with celiac disease encounter gluten, they release a protein called interleukin-2, which the test measures. This approach essentially recreates the immune reaction outside the body, allowing diagnosis without requiring patients to make themselves ill.1

Changes in Diagnostic Guidelines

Beyond new testing methods, the approach to interpreting existing tests is also evolving. In September 2025, the European Society for the Study of Coeliac Disease released updated diagnostic guidelines that represent a significant shift in how celiac disease can be confirmed in adults. These guidelines now allow doctors to diagnose celiac disease without requiring an endoscopic biopsy in certain carefully defined situations, bringing adult diagnostic standards closer to what has been practiced in pediatric medicine for over a decade.

Under the new guidelines, symptomatic adults under age 45 with extremely high levels of tissue transglutaminase antibodies (at least ten times the upper limit of normal, confirmed on two separate blood samples) may be diagnosed with celiac disease based on blood work alone. This approach recognizes that when antibody levels are elevated, the likelihood of the biopsy showing anything other than celiac disease is extremely low, around 98-99%. The guidelines include important safeguards: patients must have symptoms consistent with celiac disease, should not have warning signs suggesting other conditions, and the decision should involve shared discussion between doctor and patient about whether to proceed with or without biopsy.

This shift reflects growing evidence that very high antibody levels are extremely reliable indicators of celiac disease, making routine biopsies less necessary in these clear-cut cases. It also reduces the burden on patients who would otherwise need to undergo an invasive procedure primarily to confirm what blood tests have already strongly indicated. While these are European guidelines and adoption in the United States may take time, they represent the direction the field is moving toward more streamlined, less invasive diagnostic approaches when the evidence is sufficiently clear.2

What These Developments Mean for Patients

These advances in celiac diagnosis address longstanding problems that have kept many cases undetected or forced patients through unnecessary suffering to obtain answers. The IL-2 blood test, while not yet widely available, eliminates the need for patients to deliberately consume gluten and make themselves sick. The updated diagnostic guidelines similarly reduce the burden by allowing diagnosis without invasive procedures when blood test results are unambiguous. Together, these changes point toward a future where getting diagnosed with celiac disease doesn’t require choosing between staying healthy and getting medical confirmation.

The IL-2 test is currently in clinical trials at major medical centers and is expected to become available for routine use within the next few years, possibly even in 2026 or 2027. As these testing methods become established and guidelines continue to evolve, patients who have been avoiding diagnosis due to the gluten challenge requirement may finally have a viable path forward. For now, anyone who suspects they might have celiac disease should still pursue testing before eliminating gluten from their diet, as this remains the most straightforward route to diagnosis with currently available methods.

Contact Cary Gastro for Celiac Treatment

If you’re experiencing symptoms that suggest celiac disease or have questions about the diagnostic process, the gastroenterologists at Cary Gastroenterology can help. Our team stays current with developments in celiac diagnosis and provides comprehensive evaluation for patients with digestive health concerns. Whether you have a family history of celiac disease or simply want to understand your symptoms better, we can guide you through appropriate testing and next steps. Contact us today to request an appointment.



1https://celiac.org/2025/06/16/a-game-changer-for-celiac-diagnosis-il-2-blood-test-may-eliminate-the-need-for-gluten-challenges/
2https://onlinelibrary.wiley.com/doi/full/10.1002/ueg2.70119