36 - Instant insights: Identifying and diagnosing celiac disease (8 min) - Healthier World with Quest Diagnostics

Summary4 min read

Episode Overview

Podcast: Healthier World with Quest Diagnostics
Episode: 36 - Instant Insights: Identifying and Diagnosing Celiac Disease
Host/Expert: Dr. Mason Latsko
Date: May 4, 2026
Duration: 8 minutes

This “Instant Insights” episode delivers a fast, actionable summary on celiac disease, focusing on how clinicians can better recognize its varied presentations and leverage laboratory diagnostics to improve detection and management. Dr. Mason Latsko underscores the challenges of underdiagnosis, discusses the disease's pathophysiology, and walks through the evidence-based diagnostic cascade, including best practices for serological and genetic testing.

Key Discussion Points & Insights

1. The Challenge of Underdiagnosis

83% Misdiagnosed or Undiagnosed:
"An estimated 83% of people with celiac disease are misdiagnosed or remain underdiagnosed, leading to an average diagnosis delay of six to ten years." (00:38)
Complications of Delayed Diagnosis:
Years of “uncertain suffering” increase risk for long-term issues such as malnutrition, infertility, and malignancy.

2. Atypical and Varied Presentations

Beyond the Gut:
While GI symptoms (diarrhea, bloating, pain) are common, many adults present with:
- Unexplained iron deficiency
- Skin rashes
- Elevated liver enzymes
- Non-GI manifestations: chronic migraines, joint pain, peripheral neuropathy (01:20)
Symptom Overlap With IBS:
Many symptoms overlap with irritable bowel syndrome, highlighting necessity for heightened clinical suspicion and proper testing.

3. Pathophysiology Overview

Immune-Mediated Reaction:
“An enzyme called tissue transglutaminase or TTG modifies the key protein in gluten called gliadin… In celiac disease, the patient has a genetic predisposition that causes their immune system to incorrectly view this modified gliadin protein as a threat, triggering an autoimmune attack.” (02:17)
Autoantibody Production:
The autoimmune process leads to antibodies targeting TTG, primarily immunoglobulin A (IgA).

4. Diagnostic Markers and Testing Strategies

First-Line Serologic Markers:
- TTG IgA: Primary autoantibody marker.
- Endomysial Antibody (EMA): Used for confirmation and assessment of disease severity:
  - "If EMA is positive, the panel reflexes to perform EMA titer, which allows us to identify the severity of the disease, with low titers suggesting less severe damage or earlier stage disease and high titers strongly suggesting severe damage and active disease." (03:20)
- Both are IgA-dependent.
The Role of IgA Deficiency:
- "Another key component of testing is making sure the patient is not IgA deficient. This is relatively common in celiac disease with approximately 2.5% prevalence." (04:16)
- Total IgA Test: Assesses for deficiency. If IgA is normal, IgA-based markers are reliable; if low, they’re not.
Back-up IgG Testing:
- Used if IgA deficiency is found.
- TTG IgG and DGP IgG:
  - DGP IgG is especially sensitive in patients already on gluten-free diet, since these antibodies decrease more quickly with avoidance, making them useful for monitoring.
  - “DGP IgG is becoming increasingly important as it’s particularly sensitive in patients who have already started a gluten free diet.” (05:10)

5. Quest Diagnostics' Automated Diagnostic Cascade

Streamlined Process:
- Panel begins with TTG IgA and total IgA testing.
- If TTG IgA is positive, reflex to EMA for confirmation.
- If IgA is low, panel automatically reflexes to TTG IgG.
- "This ensures that a comprehensive workup is completed for a single sample, providing the clearest possible answers for that patient." (06:02)

6. Genetic Testing

HLA DQ2 or DQ8 Alleles:
“Virtually all patients with celiac disease have an underlying genetic predisposition… These genetic tests have a strong negative predictive value. They are most useful in ruling out the disease, especially in at-risk family members or in case of diagnostic uncertainty.” (06:36)

7. Diagnosis Confirmation and Monitoring

Next Steps:
- Positive serology: Refer to gastroenterologist.
- Definitive Diagnosis: Endoscopic biopsy for visual confirmation of villous atrophy.
- Treatment: Lifelong strict gluten-free diet.
Follow-Up:
Repeat serology (usually TTG IgA, EMA) is valuable to ensure dietary adherence and mucosal healing.

Notable Quotes & Memorable Moments

On Underdiagnosis:
"This delay isn't just a number. It represents years of uncertain suffering and an increased risk for long-term complications..." — Dr. Mason Latsko (00:54)
On Overlapping Symptoms:
“Many of these symptoms overlap with conditions like irritable bowel syndrome or IBS, which is why a high index of suspicion and proper testing is crucial for distinguishing between these diseases.” (01:55)
On Diagnostic Cascade:
“The process starts with testing for TTG IgA and total IgA… If the initial test finds that the total IgA levels are low, the panel knows that the IgA based test is unreliable, so it automatically reflexes to TTG IgG.” (05:48)
On the Patient Journey:
"Remember, for a patient who has been searching for answers for years, this isn't just a test result, it's the end of a diagnostic journey and the beginning to their recovery.” (07:30)

Important Timestamps

00:38 — Statistics on underdiagnosis and diagnostic delay
01:20 — Range of celiac disease symptoms (GI and non-GI)
02:17 — Pathophysiology explained
03:20 — Explanation of serological markers and their roles
04:16 — Prevalence and impact of IgA deficiency
05:10 — Role of DGP IgG, especially in diet monitoring
05:48 — Laboratory diagnostic cascade process
06:36 — Utility of genetic testing in celiac diagnosis
07:30 — The significance of diagnosis for patients

Summary

This expertly concise episode provides frontline clinicians with immediate, actionable insights on the hidden epidemic of celiac disease. Dr. Mason Latsko, in clear, approachable language, describes the wide clinical variability of the disease, critical steps in serologic and genetic testing, and the value of a diagnostic cascade that adapts to any patient scenario. The episode emphasizes the importance of considering celiac disease in a variety of presentations, outlines best-practice laboratory pathways, and reaffirms that accurate diagnosis is life-altering for vulnerable patients seeking answers.

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Transcript1 lines

[00:00]
A
Foreign welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from Insight as we keep you up to date on current clinical and diagnostic topics to transform lives and illuminate a path to better health. Welcome to a special episode series called Instant Insights, a podcast episode designed to give you quick and highly impactful clinical pearls in just a few minutes. Dr. I'm Dr. Mason Latsko and today we're tackling celiac disease, a serious autoimmune disease that often hides behind persistent and unexplained symptoms like chronic fatigue, bloating and iron deficiency anemia. An estimated 83% of people with celiac disease are misdiagnosed or remain underdiagnosed, leading to an average diagnosis delay of six to 10 years. And this delay isn't just a number. It represents years of uncertain suffering and an increased risk for long term complications including malnutrition, infertility and even malignancy. Celiac disease presentation is incredibly varied. While we often think of gastrointestinal symptoms like diarrhea, bloating and abdominal pain, a significant number of patients, especially adults, present with non GI symptoms. Often you'll find unexplained iron deficiency, rashes on the skin, elevated liver enzymes, and sometimes other issues seemingly unrelated like chronic migraines, joint pain and peripheral neuropathy. Many of these symptoms overlap with conditions like irritable bowel syndrome or ibs, which is why a high index of suspicion and proper testing is crucial for distinguishing between these diseases. This episode will help you understand and recognize celiac disease more effectively. We'll cover the pathophysiology of the disease and then see how we can apply laboratory testing to accurately diagnose the disease. First, let's talk about the pathophysiology of the gut. The intestinal wall is lined with finger like villi to absorb nutrients. When a healthy person consumes gluten. An enzyme called tissue transglutaminase or TTG modifies the key protein in gluten called gliadin protein, and in a healthy person this is recognized as harmless food and the modified gliadin protein is ignored. But in celiac disease, the patient has a genetic predisposition that causes their immune system to incorrectly view this modified gliadin protein as a threat, triggering an autoimmune attack. The patient with celiac makes an autoantibody against ttg. The primary TTG in the gut is called immunoglobulin A. So the first line in identifying whether or not a patient may be having a Reaction to gluten is to look for the TTG immunoglobulin A or TTG IgA. The second highly specialized marker is the endomysium antibody or ema. The endomysium is a layer of connective tissue in the gut muscle that is rich in TTG enzyme. So a positive test serves as a powerful signal that there's a specific autoimmune process happening in the gut. If EMA is positive, the panel reflexes to perform EMA titer, which allows us to identify the severity of the disease, with low titers suggesting less severe damage or earlier stage disease and high titers strongly suggesting severe damage and active disease. Both of these first line markers are IGA dependent, since we're essentially asking whether or not the patient is making an autoantibody that is IGA specific and whether this autoimmune reaction is originating in the gut using ema. So another key component of testing is making sure that the patient is not IGA deficient. This is relatively common in celiac disease with approximately 2.5% prevalence. So to test for IgA deficiency, we can test for total IgA. If the patient has an elevated or normal IgA in the blood, we can be sure that they are not IGA deficient and we can trust the results of the other initial markers. If the patient is IgA deficient, the initial assessment of TTG IgA cannot be validated since IgA isn't present in that patient. So instead we rely on backup markers that use a different antibody class, immunoglobulin G or IgG. And two different IgG tests can be used. The TTG IgG, which targets the TTG enzyme and Dgp IgG, which targets the gliadin protein or the modified gluten fragment that initiates the immune reaction. DGP IgG is becoming increasingly important as it's particularly sensitive in patients who have already started a gluten free diet. As DGP antibody levels decrease more rapidly than TTG antibodies, making it a valuable early indicator of dietary compliance. Now that we understand the role of each marker, let's see how Quest Diagnostics comprehensive panel connects them in an automated cascade. The process starts with testing for TTG IGA and total iga. From there, one of two things happens automatically. If the TTG IGA is positive, the panel reflexes to perform an EMA to confirm the autoantibodies are targeting the gut tissue. But if the initial test finds that the total IGA levels are low, the panel knows that the IGA based test is unreliable, so it automatically reflexes to TTG IgG. This ensures that a comprehensive workup is completed for a single sample, providing the clearest possible answers for that patient. One final line of tests that can be run to identify if a patient has celiac is genetic tests. Virtually all patients with celiac disease have an underlying genetic predisposition, and while it's possible to have a susceptible allele and not develop celiac, virtually everyone with celiac has a specific allele in either HLA DQ2 or HLA DQ8. So these genetic tests have a strong negative predictive value. They are most useful in ruling out the disease, especially in at risk family members or in case of diagnostic uncertainty. A positive serology cascade is a strong indicator of celiac disease and the standard next step is a referral to a gastroenterologist. A definitive diagnosis is typically made with an endoscopy biopsy to visually confirm villous atrophy in the gut. Following a confirmatory diagnosis, the treatment is strict lifelong gluten free diet. Follow up serology testing is also valuable if monitoring a patient's adherence to the diet and as the intestines heal, the antibody levels should decrease significantly. Remember, for a patient who has been searching for answers for years, this isn't just a test result, it's the end of a diagnostic journey and the beginning to their recovery. That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world one life at a time.