Advancing Wheat Immune Testing in Clinical Practice

by our educational team
February 16, 2026

Why Raw Wheat Testing Alone Can Miss Up to 1 in 5 Immune Reactions

For many clinicians, gluten is straightforward. When immune reactivity to wheat is present, dietary elimination is the appropriate clinical response. That principle remains unchanged.

What has evolved is our understanding of how the immune system recognizes wheat.

WheatBurden™ (Formerly Array 3X) is designed to reflect the reality that the immune system does not respond to wheat as a single, static antigen. Wheat proteins are structurally modified through hydration, fermentation, baking, and cooking—and those modifications can meaningfully influence immune recognition. Testing only raw wheat components does not always capture this complexity.

Importantly, unlike food sensitivity panels, the absence of reactivity to specific processed wheat markers should not be interpreted as permission to consume those forms, but rather as information about how—and whether—the immune system is recognizing structurally modified wheat proteins.

This article outlines how processed wheat testing fits into clinical decision-making and how WheatBurden™ is intended to be used in practice.

Why Raw Wheat–Only Testing Can Miss Immune Reactivity

Traditional wheat immune testing focuses on antibodies to raw wheat components, such as native gluten and non-gluten proteins. This approach remains clinically valuable and continues to serve as an important foundation for identifying wheat-related immune responses. However, it represents only part of the immune picture.

In practice, patients are not consuming raw wheat flour. Wheat is most commonly encountered after it has been hydrated, fermented, baked, or cooked—processes that substantially alter protein structure and immune recognition. When testing is limited to raw wheat antigens, immune responses triggered by structurally modified wheat proteins may go undetected.

Cyrex research evaluating immune responses to both raw and processed wheat forms highlights this distinction clearly among individuals with documented wheat immune reactivity:

Approximately 70% of individuals who demonstrate immune reactivity to wheat flour also show reactivity to bread proteins.
Importantly, an additional ~20% of individuals produce IgG and/or IgA antibodies to processed wheat products despite testing negative to raw wheat antigens.

For the 20% of individuals, raw wheat–only testing may underestimate immune activation. Clinically, this can present as persistent inflammation, incomplete symptom resolution, or continued immune signaling despite dietary modifications guided by conventional test results. In such cases, symptoms may be attributed to non-dietary causes when, in reality, immune recognition of processed wheat antigens remains unaddressed.

Including processed wheat antigens in immune testing provides greater resolution by aligning laboratory assessment with real-world exposure. This approach helps clinicians identify immune reactivity patterns that would otherwise remain unexplained and supporting more informed clinical decision-making when wheat sensitivity is suspected but not fully captured by raw antigen testing alone.

Clinical Interpretation: What Processed Wheat Markers Are (and Are Not)

WheatBurden™ is designed to complement established clinical frameworks, not to redefine them. The presence of processed wheat markers does not alter the fundamental role of gluten avoidance when immune reactivity is identified.

A positive immune response to any wheat-related marker, whether directed at raw wheat components or processed wheat antigens, continues to support gluten avoidance as the appropriate clinical recommendation. This principle remains consistent across all components of the panel.

As outlined in Cyrex clinical guidance, patients who demonstrate immune reactivity to wheat peptides should continue gluten avoidance even if specific bread extracts do not show reactivity. Antibody class, magnitude of response, and clinical context remain central to interpretation, with IgA elevations warranting particular attention due to their association with mucosal immune activation.

Why Representative Wheat Products Are Used

Wheat-based foods vary substantially based on:

Wheat source and cultivar
Fermentation duration and method
Additives and processing aids
Heat exposure and cooking technique

Testing representative categories—such as sourdough, sprouted bread, pasta, and yeast-free flatbreads—allows clinicians to assess patterns of immune recognition related to processing. These categories are not intended to reflect brand-level recommendations or individualized food approval.

The clinical question being addressed is whether immune reactivity is limited to native wheat proteins or extends to proteins modified through processing.

Practical Guardrails for Clinical Use

WheatBurden™ is intended to be interpreted within clear, clinically consistent parameters that align with how immune markers are already used in practice. The panel is designed to support decision-making, not override it.

Raw Wheat Reactivity	Processed Wheat Reactivity	Clinical Considerations
Positive	Positive	Any positive wheat, gluten peptide, or processed wheat marker continues to support gluten avoidance as the appropriate clinical recommendation. Immune recognition of wheat—regardless of the form tested—indicates that exposure is relevant to the patient’s inflammatory or immune profile.
Negative	Positive	Positive processed wheat markers with negative raw wheat markers suggest immune reactivity that may not be captured through conventional testing alone. In these cases, processed wheat antigens can help explain persistent symptoms, incomplete clinical response, or ongoing immune activation despite prior dietary guidance based on raw wheat results.
Positive	Negative	Negative processed wheat markers with positive wheat peptide markers do not negate the need for gluten avoidance. As outlined in Cyrex clinical guidance, immune reactivity to wheat peptides reflects recognition of core wheat antigens and remains clinically actionable regardless of reactivity to specific bread extracts.

Antibody class remains a critical component of interpretation.

IgA elevations	Warrants particular caution due to their association with mucosal immune activation and potential tissue injury.
IgG elevations	Reflect immune recognition and inflammatory signaling and may correlate with symptom burden or chronic immune activation over time.

In practice, WheatBurden™ supports a pattern-based interpretation, where results are evaluated in context rather than in isolation.

Dietary recommendations remain the responsibility of the practitioner and should always be informed by the full clinical picture. WheatBurden™ provides additional clarity where needed, helping clinicians make more confident decisions without altering established standards of care.

The Clinical Takeaway

Patients consume wheat in baked, fermented, and cooked forms—not as raw flour. Testing strategies that reflect real-world exposure improve diagnostic accuracy and reduce the risk of missed immune activation.

WheatBurden™ aligns immune testing with how wheat is actually encountered by the immune system. It provides clinicians with a more complete view of wheat immune reactivity, supports earlier identification of false negatives, and enables more confident clinical decision-making.