What if some of the immune activity we’re looking for isn’t showing up where we expect to find it?
In this episode, I sit down with Robyn Puglia of Cyrex Laboratories to explore TG6, lymphocyte patterns, and early autoimmunity—and specialized testing many practitioners may not realize is available through Cyrex Array 3, the Lymphocyte Map, and Array 5.
We look at neurological manifestations of gluten-related disease, what different immune cell populations may add to the clinical picture, and how autoantibodies can sometimes appear before autoimmune disease is diagnosed.
The bigger question: Can seeing more of the immune story help us ask better questions about what may be driving a complex presentation?
Robyn Puglia’s work with celiac disease, neurological symptoms, autoimmunity, and complex chronic illness pushed her to ask what the immune system might be telling us beyond a routine workup. Today, as Vice President of Practitioner Education at Cyrex Laboratories, she teaches practitioners how to think about specialized immune testing without treating an abnormal biomarker as a diagnosis.
Most practitioners know tissue transglutaminase 2 (TG2) from celiac testing. Tissue transglutaminase 6 (TG6) has been studied in gluten-related neurological disorders, particularly gluten ataxia. (Hadjivassiliou 2019)
TG6 isn’t part of routine guideline-supported celiac screening, but it highlights an important point: gluten-related immune disease can have extraintestinal manifestations, including neurological symptoms. (Mearns 2019) (Rubio-Tapia 2023)
Array 3 evaluates antibody reactivity to multiple wheat-associated antigens and transglutaminases, including TG6.
It provides a broader look at wheat-associated immune reactivity than conventional celiac serology. It shouldn’t replace established evaluation for celiac disease or wheat allergy; the value of additional biomarkers depends on the clinical question and the evidence supporting their intended use. (Rubio-Tapia 2023) (Leonard 2017)
The Cyrex Lymphocyte Map examines populations and subsets of T cells, B cells, and natural killer cells.
Instead of asking whether one value is simply high or low, Robyn looks at the pattern and asks what might explain it. Infection? Medication effects? Immune dysfunction? Another clinical process?
The pattern isn’t the diagnosis. It helps sharpen the investigation.
Yes. In several autoimmune diseases, researchers have detected disease-associated autoantibodies before patients meet formal diagnostic criteria—sometimes years earlier. (Ma 2017)
Cyrex Array 5 evaluates multiple tissue-associated autoantibodies that Robyn discusses in this context. But an autoantibody isn’t a crystal ball. Its significance depends on the specific marker, the patient, and the evidence supporting its clinical use. (Ma 2017)
Yes. Cyrex offers the specialized tests discussed in this episode, including Array 3, the Lymphocyte Map, and Array 5, along with additional testing related to mucosal immunity and barrier function.
The important question isn’t, “How much can I test?”
It’s “What am I trying to understand, and will this result change what I do next?”
02:42 — The patients who pulled Robyn deeper into immunology
How celiac disease and unexplained illness changed her approach to complex patients.
11:41 — TG6: When gluten becomes a brain conversation
Why gluten-related immune activity isn’t necessarily confined to the gut.
13:49 — Are we asking enough questions about wheat?
The thinking behind Cyrex Array 3 and its broader look at wheat-associated antigens and transglutaminases.
28:29 — What if autoimmunity starts before the diagnosis?
Tissue-associated autoantibodies, Array 5, and preclinical autoimmunity.
33:49 — Your lymphocyte count isn’t the whole story
T cells, B cells, natural killer cells, and the Cyrex Lymphocyte Map.
39:25 — The abnormal result is where the investigation starts
How immune patterns can generate better clinical questions.
44:20 — Stop looking for one perfect root cause
Robyn’s “aggregate gains” approach to complex illness.
50:49 — What else can we see in the immune system?
Tissue autoantibodies, mucosal immunity, and barrier biomarkers.
57:42 — When neurological symptoms change the workup
Why brain symptoms may require a broader metabolic, vascular, and immune picture.
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The views expressed on this podcast are those of the hosts and the guests, and they don't necessarily reflect the views of FullScript or any affiliated organizations. This podcast is for informational and educational purposes only, and it's not intended to be medical advice. For your safety, always check with your healthcare provider before making any changes to your healthcare routine.