The Truth About Genetic Testing for Celiac Disease
Why a Positive Result Doesn’t Mean You Have the Disease — and When This Test Is Actually Useful
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One of the tests that causes the most confusion among my patients is the genetic test for celiac disease.
Many people stop eating gluten because this test comes back positive, and in many cases, that’s a mistake.
What is this test? What is it really for? What does it mean if it’s positive or negative? In which patients should it be ordered?
But before we go on, subscribe to my blog — it’s all about digestive health, explained by a medical specialist in gastroenterology.
Celiac disease is an inflammation triggered by eating gluten, caused by our own immune system attacking the cells that line the small intestine. This inflammation prevents the intestine from functioning properly, leading to poor absorption of nutrients and loss of nutrients through the stool. As a result, patients with celiac disease may experience weight loss, iron and vitamin deficiencies, and digestive symptoms such as bloating, diarrhea, and other discomforts.
Our body has a system of cells that protect us from “bad bugs” like bacteria, fungi, and viruses — this is our immune system. The digestive tract is constantly exposed to the outside world, so it contains a specialized intestinal defense system that acts against invading microorganisms.
Imagine there’s a criminal (a bacterium) hiding in a forest (our body). In the forest, a police officer (T lymphocyte) and his dog (macrophage) are patrolling. The dog smells something suspicious, ventures into the woods, and finds the criminal. It can’t arrest him, but it can bring back evidence — it bites off a piece of the criminal’s clothing and brings it to the officer, who alerts the others, and an arrest operation is launched.
In this metaphor, the dog is a macrophage — an immune cell that detects threats like bacteria. When it finds one, it takes a piece of the microorganism in its “mouth” and presents it to the “police officer” — the T lymphocyte. The T lymphocyte then triggers an inflammatory response to eliminate the intruder.
The “mouth” of the dog — the structure the macrophage uses to present the threat — is made up of proteins called HLA. These proteins “display” pieces of microorganisms or other substances so that immune cells can recognize them.
Gluten, a protein found in wheat and other grains, breaks down into fragments during digestion. These fragments can be mistaken by our macrophages. The macrophages (dogs) collect them, present them using their HLA proteins (their “mouths”), and show them to the T lymphocytes (police). If the immune system makes a mistake, the T cells treat gluten as a real threat and trigger strong inflammation that damages the intestine. Very simply put, that’s celiac disease.
The “mouths” that allow this presentation of fragments are HLA proteins, which vary greatly between individuals — like dogs having big, small, narrow, or wide snouts. These differences are inherited from our parents.
99% of people with celiac disease have an HLA type that tends to present gluten fragments and activate the immune system. These are HLA DQ2 and DQ8. But — and this is key — these HLA types only indicate a predisposition, not a diagnosis.
1 in every 4 or 5 people has these HLA types linked to celiac disease… but most will never develop it.
So, if the genetic test is positive, it means you could develop celiac disease, but it doesn’t mean you have it. You have a predisposition, but you may never develop the disease. The risk depends on your specific HLA combination, ranging from about 1% (low-risk) to 25–30% (high-risk).
If the genetic test is negative (you don’t have HLA DQ2 or DQ8), it almost completely rules out the disease — fewer than 1% of celiac patients lack these genes. This is why the test’s greatest value lies in a negative result: it rules out the disease, but a positive result does not confirm it.
Celiac disease is diagnosed in other ways — through blood tests to detect specific antibodies, intestinal biopsies, and clinical evaluation. The genetic test is reserved for uncertain cases, such as:
Patients with very typical symptoms of celiac disease but normal or inconclusive antibody and biopsy results.
People who stopped eating gluten without a formal diagnosis and can no longer undergo reliable standard testing.
In summary:
99% of people with celiac disease have genes coding for special HLA proteins (DQ2 or DQ8).
But 1 in 4 or 5 healthy individuals also carry these HLA types.
A positive genetic test shows predisposition, not diagnosis.
A negative test virtually rules out celiac disease.
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