Food sensitivity re-testing: evidence for the most accurate protocol

When your patient's immune tolerance has improved and it's time to answer the question "have they re-gained tolerance to selected foods to which they were sensitive?", a fascinating study published in GUT, An International Journal of Gastroenterology and Hepatology (BMJ Group) offers evidence for the best way to stage a re-test of food sensitivity. The authors' specific intent was to investigate the dynamics of the response to a gluten challenge in patients with celiac disease who had been on a gluten-free diet:

"Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed."

They fed 20 adults with biopsy-proven celiac disease a gluten dose of 3 or 7.5 g per day for 14 days (yikes), followed by data collection on days 3, 7, 14 and 28 after starting the gluten challenge. They performed duodenal biopsies before the challenge and at days 3 and 14, measuring the villous height to crypt depth ratio (Vh:Cd) and the intraepithelial lymphocyte (IEL) count/100 enterocytes ratio. Importantly for the purpose of re-testing food sensitivity in general they assessed antibodies to tissue transglutaminase and deamidated gliadin peptides. They also included the lactulose to mannitol ratio (LAMA) and symptoms at each visit. Their very interesting data offer helpful parameters:

"Significant reduction in Vh:Cd (2.2–1.1, p<0.001) and increase in IELs (32.6–51.8, p<0.001) were seen from baseline to day 14. Antibody titres increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses."

There are valuable points to be taken. The most important for the purpose of food sensitivity re-testing is the trajectory of antibodies following the allergen (gluten) challenge: A marked increase in the antibodies tested was not observed until the 28 day measurement. This means that re-testing much earlier than 25-30 days after a challenge significantly increases the risk of false negatives.Additionally, I have not found the lactulose-mannitol ratio to be an accurate indicator of loss of gut barrier integrity (intestinal permeability), and these investigators saw no significant change throughout their trial. I much prefer the Intestinal Antigenic Permeability Screen offered by Cyrex Laboratories. These authors conclude:

"14 day GC at ≥3 g of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a 2-week GC."

Clinical note: though we have to ask to what degree  a gluten challenge study applies to other food sensitivities this does suggest a way to go forward. Unless future evidence indicates otherwise, I believe that I am minimizing the risk of misleading false negatives in food sensitivity re-testing by having my patients consume the foods in question for a week, then waiting until days 25-30 to have their blood drawn.One other point specific to gluten: the antibodies peaked at day 28, they did not subside then. Others have documented the persistence of gluten antibodies until 240 days after gluten avoidance is initiated, and the subsidence of GI symptoms does not insure that important non-celiac inflammatory effects are resolved within a month.