When "Low" Celiac Blood Tests Still Point to Celiac Disease (+Video)

Celiac.com 12/05/2025 - Many people are tested for celiac disease using blood tests that look for antibodies against tissue transglutaminase 2. High values are well known to match up with damage in the small intestine and often allow doctors to diagnose without a biopsy in select settings. Far less clear is what to do when results are just above the test cutoff (“low positive”) or sit just below it (“borderline negative”). This study followed a carefully defined group of adults to learn how often those softer results still signal true celiac disease or an early stage that deserves close follow-up.

Who Was Studied and How

Researchers examined 311 adults who either had symptoms that raised concern for celiac disease or had a family history of the condition. Everyone had blood tests and small-bowel biopsies. Blood testing included:

• Antibodies against tissue transglutaminase 2 (with the manufacturer’s cutoff for positivity at 7.0 units per milliliter).
• Endomysial antibodies, a highly specific companion test.
• Genetic testing for human leukocyte antigen types linked to celiac disease (human leukocyte antigen DQ2 or DQ8).

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The team defined “low positive” as 7.0–14.0 units per milliliter and “borderline negative” as 3.0–6.9 units per milliliter. Beyond routine biopsy reading, they also looked for two tissue signs that mark celiac disease activity even at early stages: tissue transglutaminase 2-targeted antibody deposits in the intestinal lining and an increased number of a specific type of intraepithelial lymphocyte (called gamma delta cells).

Key Results at a Glance

• Low positive results were often real celiac disease. Among people with low positive transglutaminase 2 antibodies, almost nine in ten received a celiac disease diagnosis after combining biopsy, special tissue markers, and clinical response.
• Borderline negative did not rule out disease. In the borderline negative group, more than one in three were ultimately diagnosed with celiac disease. Among those who were also positive for endomysial antibodies, nearly four in five had celiac disease.
• Early activity was common even without a firm diagnosis. In people with borderline negative results who were not diagnosed, almost one in three still showed celiac-specific tissue changes or genetic risk that suggested an early or developing stage.
• Very high values were decisive. Every participant whose transglutaminase 2 antibody level reached at least 3.2 times the upper limit of normal received a diagnosis of celiac disease.

What “Low Positive” Really Means

A number just above the test cutoff can feel uncertain. This study shows that, in a specialist setting, low positive values often reflect genuine disease rather than test noise. Some people with low positive results did not yet have the classic level of intestinal damage, but they did have celiac-specific tissue deposits or increased gamma delta lymphocytes, and they improved or showed clear changes when gluten was removed or reintroduced under supervision. In other words, a low positive result can catch celiac disease early, before the intestinal lining is more severely injured.

What “Borderline Negative” Can Hide

Borderline negative numbers are below the standard cutoff, yet this study found that they can still be meaningful, especially when paired with endomysial antibody positivity or celiac-linked genes. A substantial portion of these individuals either already met criteria for celiac disease or showed early markers that warranted close follow-up. For families with a history of celiac disease, a borderline negative result should not be brushed off, particularly if symptoms are present.

The Special Role of Endomysial Antibodies

Endomysial antibodies were the tie-breaker in many ambiguous cases. When endomysial antibodies were positive alongside a low positive transglutaminase 2 result, every single person in that group had celiac disease. Even within the borderline negative range, a positive endomysial antibody result greatly raised the chance of a true diagnosis. While endomysial testing is more specialized and operator-dependent, this study supports using it as a second step whenever first-line results are borderline or only slightly positive.

How Doctors Might Use These Findings

• Treat results as a continuum, not a switch. Numbers near the cutoff should be interpreted with clinical judgment, genetics, and—when available—special tissue markers, not dismissed as “negative.”
• Repeat testing on a gluten-containing diet. For borderline or low results, retesting after several months can show whether antibodies are trending upward and can avoid missed or delayed diagnoses.
• Use endomysial antibodies to clarify. When available, endomysial testing can convert uncertainty into clarity, especially in the borderline zone.
• Do not forget the biopsy and tissue markers. Multiple biopsy samples, careful orientation, and, where possible, testing for transglutaminase 2-targeted deposits and gamma delta lymphocyte counts can reveal early disease.

Strengths and Limits

This study’s strengths include a clearly described adult cohort, comprehensive blood testing, and careful small-bowel evaluation with both standard pathology and celiac-specific tissue markers. It also included people tested because of symptoms and people screened due to family history. Limitations include the lack of data on medicines that might blunt antibody production, no measurement of deamidated gliadin peptide antibodies, and the fact that all participants already had a higher chance of disease than the general population. The results therefore guide specialist practice but should be applied thoughtfully in broader settings.

What This Means for People with Celiac Disease or at Risk

If your transglutaminase 2 antibody result is only slightly above the cutoff or just below it, do not assume it “does not count.” In this study, many people in those gray zones either had celiac disease already or showed early immune activity that called for close follow-up. If you also test positive for endomysial antibodies, the likelihood that this reflects true celiac disease is high. If you have symptoms or a family history, ask about repeat testing while still eating gluten, consider endomysial antibody testing, and discuss whether a biopsy and, if available, celiac-specific tissue markers are appropriate. Early identification matters: catching celiac disease before advanced intestinal damage develops can speed healing, reduce complications, and improve day-to-day wellbeing.

Bottom Line

Celiac blood tests live on a spectrum. “Low positive” often means real disease, and even “borderline negative” can signal celiac disease—especially when endomysial antibodies are present or when early tissue markers are detected. For patients and families, this supports a proactive approach: pair antibody results with symptoms, genetics, endomysial testing, and thoughtful biopsy strategies. For people living with celiac disease or at high risk, that approach can shorten the road to answers and help you start healing sooner.

Read more at:  onlinelibrary.wiley.com

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