Gluten Challenge
Blood testing (tTG-IgA) is the first step in screening for celiac disease when it is suspected. However, if a gluten-free diet has already been started, the blood test becomes unreliable and may show a false-negative result. In this situation, a healthcare provider may recommend a gluten challenge to diagnose celiac disease.
If the tTG-IgA test comes back negative because the person has not been eating gluten, a genetic test called HLA typing can help decide whether more testing is needed. Almost all people with celiac disease (99%) have at least one of two specific HLA genes: HLA‑DQ2 or HLA‑DQ8. If a person does not have either of these genes, it is very unlikely that they will develop celiac disease, so further testing is not necessary.
About 30% of adults in North America have the HLA‑DQ2 or HLA‑DQ8 gene, but only around 4% of people with these genes will develop celiac disease. Among first-degree relatives, 80% of the other family members are likely HLA DQ2 and/or DQ8 positive, but the rate of celiac disease in first-degree relatives ranges up to 15%. This shows that HLA genes only indicate a person’s risk for celiac disease, while celiac blood tests like tTG‑IgA or EMA are used to detect active celiac disease.
If the HLA DQ2 and/or DQ8 are positive, the patient can start a gluten challenge under medical supervision
Classical Gluten Challenge
This type of challenge can be hard to tolerate for some patients; therefore, some may be resistant to this approach.
- The adult is asked to eat 6-10 grams of gluten a day, about 2-3 slices of wheat bread a day, for 6-8 weeks.
- This dose of gluten can be gradually built up over the first week to make it easier to tolerate.
- A repeat celiac blood test is done after the challenge.
Modified Gluten Challenge
A newer approach uses a smaller amount of gluten during the challenge. This lower dose may be easier for people to tolerate and has still been shown to work for diagnosing celiac disease.
- The adult is asked to eat 3 grams of gluten a day, about 1.5 slices of wheat bread a day, for at least 6 weeks. In some cases, it may take longer for the body to produce antibodies.
- A repeat celiac blood test is done after the challenge.
Symptomatic Patient
- Consider repeating the celiac blood test 4 weeks after starting the gluten challenge
- If the tTG-IgA is positive, there is a strong chance of celiac disease, and the person should be referred to a gastroenterologist. They should continue eating gluten while waiting for the appointment.
- If the tTG‑IgA test is negative, the gluten challenge should continue, and the celiac test can be repeated eight weeks later (twelve weeks from the start).
- If the tTG-IgA is still negative, celiac disease is unlikely. However, some people can have celiac disease even with a negative test, so a gastroenterologist may decide whether an upper endoscopy with biopsies is needed.
It may also be helpful to repeat the tTG‑IgA test again in 6-12 months while the person continues to eat gluten.
Asymptomatic Patient
- Continue eating gluten for up to eight weeks before repeating the celiac blood test.
- If the tTG‑IgA test is positive, there is a strong chance of celiac disease, and a referral to a gastroenterologist is needed. The person should keep eating gluten while waiting for the appointment.
- If the tTG-IgA test is negative, the gluten challenge should continue, and the celiac blood test can be repeated 6 weeks later.
- If the tTG-IgA test is still negative, celiac disease is unlikely. However, some people can have celiac disease even with a negative test, so a gastroenterologist may decide whether an upper endoscopy with biopsies is needed.
It may be helpful to repeat the tTG-IgA test again in 6-12 months while the person continues to eat gluten.
Pediatric Considerations
A gluten challenge is not recommended for children during certain stages of development:
- Before age 5
- Before their permanent teeth come in
- During the pubertal growth spurt
The modified gluten challenge (described above) may work just as well for children as it does for adults. If a child develops symptoms while eating gluten, the gluten challenge should continue, and celiac blood test should be repeated after 6 weeks. If the child has no symptoms and the tTG-IgA test is negative, they should continue to eat gluten.
References:
Singh A, Kleinhenz J, Brill H, et al. A Clinician’s Guide to Gluten Challenge. J Pediatr Gastroenterol Nutr. 2023;77(6):698-702.
