Understanding Your Blood Tests and Biopsy

You’ve been through testing, blood draws, maybe an endoscopy, definitely some waiting. Now you’re looking at results with medical jargon you’ve never seen. Here’s a plain-language guide to understanding what your tests mean.

The Blood Tests

Celiac diagnosis typically starts with blood work looking for specific antibodies. These are proteins your immune system makes in response to gluten.

tTG-IgA (Tissue Transglutaminase)

This is the primary screening test for celiac disease.

What it measures: Antibodies to tissue transglutaminase, an enzyme involved in gluten processing.

Normal range: Below 4 U/mL (varies slightly by lab).

What high means: Your immune system is reacting to gluten. Strongly suggestive of celiac disease.

How high matters: Very high levels (more than 10x the upper limit) are highly predictive of celiac, some guidelines allow diagnosis without biopsy in these cases.

Caveat: About 2-3% of people have IgA deficiency, which makes this test falsely negative. If your total IgA is low, the tTG-IgA can’t be trusted.

Total IgA

Usually tested alongside tTG-IgA.

What it measures: Your overall IgA antibody levels.

Why it matters: If this is low, you have IgA deficiency, and the tTG-IgA test isn’t reliable. Your doctor should order IgG-based tests instead.

DGP (Deamidated Gliadin Peptide)

Sometimes tested alongside tTG.

What it measures: Antibodies to a specific part of gluten.

When it’s used: More reliable in young children and in people with IgA deficiency.

What high means: Another marker suggesting celiac disease.

EMA (Endomysial Antibodies)

A highly specific test, but not always ordered.

What it measures: Antibodies targeting the lining of the intestine.

What positive means: Very strong evidence of celiac disease (high specificity).

Why it’s less common: More expensive and requires more expertise to read.

What Your Blood Test Results Mean

Negative tests + no symptoms: Probably not celiac. But if you have significant symptoms, discuss further testing.

Negative tests + symptoms: Could be celiac with IgA deficiency, early celiac, or something else. Consider IgG testing, genetic testing, or monitoring.

Positive tTG-IgA, moderate elevation: Strong suspicion of celiac. Biopsy usually recommended for confirmation.

Positive tTG-IgA, very high (10x+ normal): Very strong evidence. Some guidelines allow diagnosis without biopsy, especially in children with symptoms.

Positive multiple tests: The more markers that are positive, the more certain the diagnosis.

The Endoscopy and Biopsy

Blood tests suggest celiac, but biopsy confirms it. An endoscopy (EGD) lets the doctor look at your small intestine and take tissue samples.

What Happens

• You’re sedated (usually conscious sedation)
• A thin tube with a camera goes down your throat to your small intestine
• The doctor takes tiny tissue samples (biopsies) from the duodenum
• The whole thing takes 15-30 minutes
• You don’t feel the biopsy, there are no pain receptors there

The Marsh Score

The biopsy tissue is examined for damage. Results are often reported using the Marsh classification:

Marsh 0: Normal. No damage.

Marsh 1 (Infiltrative): Increased intraepithelial lymphocytes (immune cells in the lining). Possible early celiac or other causes.

Marsh 2 (Hyperplastic): Increased lymphocytes + crypt hyperplasia (changes in the tissue structure). Suggestive of celiac.

Marsh 3 (Destructive): Villous atrophy, the finger-like projections that absorb nutrients are damaged or flattened.

• Marsh 3a: Partial villous atrophy
• Marsh 3b: Subtotal villous atrophy
• Marsh 3c: Total villous atrophy

Marsh 3 (any subtype) with positive blood work = confirmed celiac disease.

Patchy Damage

Here’s something frustrating: celiac damage can be patchy. The doctor takes samples from a few spots, but they might miss affected areas. This is why multiple biopsies (4-6 is recommended) from different locations are important.

If your blood work is positive but biopsy is negative, discuss with your doctor whether more biopsies or follow-up testing is warranted.

Genetic Testing

Celiac disease requires specific genes to develop:

• HLA-DQ2 (present in about 95% of celiacs)
• HLA-DQ8 (present in most of the remaining 5%)

What Genetic Testing Tells You

Positive for DQ2 or DQ8: You can develop celiac disease. This doesn’t mean you have it or will get it, about 30-40% of the general population has these genes.

Negative for both: You almost certainly don’t have celiac disease and won’t develop it. This can rule out celiac definitively.

When It’s Useful

• Ruling out celiac in uncertain cases
• Testing family members who might be at risk
• If you’ve already gone gluten-free before testing (genetic tests don’t require you to be eating gluten)

Follow-Up Testing

After diagnosis, you’ll have periodic blood work:

First Year

Usually at 6 months and 12 months post-diagnosis. Your antibody levels should be dropping as you heal.

tTG-IgA going down: Great. Healing is happening.

tTG-IgA not dropping: Possible ongoing gluten exposure (hidden sources, cross-contamination). Time to investigate.

Ongoing

Most doctors recommend annual blood work. Even long after diagnosis, monitoring helps catch accidental exposure or complications.

Repeat Biopsy

Not always necessary, but sometimes done:

• If you’re not responding to the diet
• To confirm healing (especially if you were very damaged)
• Before stopping a trial of the diet (though this is rarely recommended)

What About Home Tests?

Home celiac tests exist. They’re generally not recommended for diagnosis because:

• False negatives are common
• False positives happen
• They don’t replace proper medical evaluation
• They can’t tell you about the extent of damage

If you’ve taken a home test and it’s positive, follow up with a doctor. If it’s negative but you have symptoms, still follow up with a doctor.

A Note on Testing While Gluten-Free

Here’s a crucial point: blood tests and biopsy only work if you’re eating gluten.

If you’ve already stopped eating gluten, your antibody levels drop and your intestine starts healing. This can lead to false-negative results.

If you’re already gluten-free and need testing:

• Genetic testing still works (genes don’t change)
• A “gluten challenge” may be required (eating gluten for weeks before testing)
• Discuss with your doctor before changing your diet

The gluten challenge is unpleasant. Many people feel terrible reintroducing gluten. But it may be necessary for definitive diagnosis.

Understanding Your Numbers

When you get results, you might see something like:

tTG-IgA: 87 U/mL (reference range: less than 4 U/mL)

This means your level is 87, and normal is below 4. You’re about 22 times the upper limit of normal, a strongly positive result.

Or:

Biopsy: Small bowel mucosa with increased intraepithelial lymphocytes and subtotal villous atrophy consistent with celiac disease (Marsh 3b).

This means your tissue shows significant damage consistent with celiac.

Ask your doctor to explain your specific results. You deserve to understand what’s happening in your body.

The Bottom Line

Tests confirm what’s happening. They’re not a judgment, they’re information.

A positive celiac diagnosis means you have an answer. It explains symptoms. It gives you a path forward. And while the dietary change is significant, at least you know what you’re dealing with.

Understanding your tests helps you participate in your own care. You’re not just a passive recipient of medical jargon, you’re an informed patient who knows what their numbers mean.