How Celiac Disease Works: An Accessible Explanation

When someone asks “what’s celiac disease?” you probably say something like “I can’t eat gluten.” That’s true, but it’s only the surface. Here’s what’s actually happening in your body.

The Players

Gluten: A protein found in wheat, barley, and rye. It’s what makes bread dough stretchy and chewy.

Gliadin: The specific part of gluten that triggers the celiac response. When we say “gluten causes celiac,” we really mean gliadin.

Your immune system: The defense network that protects you from threats. In celiac disease, it misidentifies gluten as dangerous.

Your small intestine: Where nutrients from food get absorbed. Specifically, the duodenum (the first section).

Villi: Tiny finger-like projections lining your small intestine. They increase surface area for nutrient absorption. Think of them like shag carpet vs. flat carpet, more surface = more absorption.

Tissue transglutaminase (tTG): An enzyme in your intestinal lining. It’s supposed to help with tissue repair, but in celiac, it becomes a target.

HLA-DQ2/DQ8: Genes that shape your immune response. About 30-40% of people have these genes, but only 2-3% of those develop celiac. They’re necessary but not sufficient.

What Happens When You Eat Gluten

Step 1: Gluten Arrives

You eat bread (or pasta, or beer). Your digestive system breaks it down, but gluten is difficult to fully digest. Partially broken-down gliadin peptides make it through to your small intestine.

Step 2: Crossing the Barrier

In celiac, the intestinal barrier is more permeable (“leaky gut”). Gliadin peptides cross into the tissue beneath the intestinal lining where immune cells live.

Step 3: tTG Gets Involved

Tissue transglutaminase chemically modifies the gliadin peptides. This modification makes them more recognizable to the immune system, like putting a “threat” flag on them.

Step 4: Immune Activation

Here’s where the HLA genes matter. If you have HLA-DQ2 or DQ8, your immune cells recognize the modified gliadin as dangerous. Immune cells called T-cells get activated.

Step 5: The Attack

The activated immune system attacks:

• The gliadin peptides
• The tTG enzyme (because it’s now associated with “danger”)
• The tissue where both are found (your intestinal lining)

This is why celiac is “autoimmune”, your immune system attacks your own tissue, not just the foreign gluten.

Step 6: Damage

The immune response damages the villi. They become flattened (villous atrophy). With damaged villi:

• Nutrient absorption drops
• Inflammation increases
• Symptoms appear

Step 7: Recovery (If You Stop Gluten)

When you remove gluten, the trigger is gone. The immune response calms. The villi slowly regrow. This takes weeks to years.

But if you eat gluten again, the whole cycle starts over.

Why It’s Autoimmune

Celiac disease is autoimmune because your body attacks itself. The tTG-IgA antibodies that we test for are your immune system making weapons against your own enzyme.

Other autoimmune diseases work similarly, different triggers, different targets, but the same basic problem: immune friendly fire.

Why Genes Aren’t Everything

HLA-DQ2/DQ8 genes are necessary for celiac disease. Without them, you can’t develop it.

But having the genes isn’t sufficient. Most people with these genes never develop celiac.

What else matters?

We don’t fully know. Likely factors:

• Environmental triggers (infections, especially gut infections)
• Gut microbiome composition
• Age at gluten introduction
• Amount of gluten consumed
• Other genetic factors beyond HLA

Celiac often appears after a trigger: a stomach bug, stress, surgery, pregnancy. Something tips the balance.

Why You Can’t Outgrow It

Some food sensitivities fade over time. Not celiac.

Once your immune system has “learned” to recognize gluten as a threat, it doesn’t forget. The memory cells persist. If you go gluten-free for years and then eat gluten, the response picks up right where it left off.

This is permanent. There’s no desensitization. The only treatment is lifelong avoidance.

Why Symptoms Vary

If gluten causes intestinal damage, why don’t all celiacs have digestive symptoms?

Different sensitivity levels: Some people’s immune systems mount stronger responses than others.

Extent of damage: More damage = more symptoms, generally. But damage location matters too.

Extra-intestinal effects: The inflammation can affect other systems: skin (dermatitis herpetiformis), neurological (brain fog, neuropathy), joints, liver.

Nutrient deficiencies: Symptoms might come from what you’re not absorbing: iron (fatigue), calcium/vitamin D (bone issues), B12 (neurological).

Other concurrent issues: Many celiacs have other conditions (lactose intolerance, other autoimmune diseases) that contribute to symptoms.

What This Means for You

Understanding the mechanism helps you understand why:

Strict avoidance is necessary. The immune response triggers from small amounts. You can’t “just have a little.”

Damage heals with time. Your intestine can regenerate. But it takes time, and ongoing exposure prevents healing.

Symptoms might not match damage. Some people have significant damage with few symptoms. Follow the diet regardless.

The disease doesn’t go away. Even when you feel better and your blood tests normalize, you still have celiac. You still need to avoid gluten.

It runs in families. First-degree relatives share genes and should be screened.

The Future

Researchers are working on:

• Enzymes that break down gluten before it reaches the intestine
• Medications that block the immune response
• Vaccines that might induce tolerance

None are approved yet. For now, the diet is the treatment.

But understanding grows. There’s hope that someday “celiac disease” might mean something you manage with medication, not just restriction.

Until then, you know what’s happening, and knowledge helps.

A Summary

1. You eat gluten
2. Gliadin peptides reach your intestine
3. tTG modifies them
4. Your HLA genes present them to immune cells
5. Your immune system attacks the gluten, the tTG, and your intestinal lining
6. Your villi flatten, absorption drops, symptoms appear
7. Remove gluten → healing
8. Reintroduce gluten → cycle repeats

That’s celiac disease. An inappropriate immune response to a protein, damaging your own tissue, fixable only by removing the trigger.

Now you can explain it to anyone who asks why you can’t just “have a little.”