Systemic Immune Response Discovered</FONT COLOR>
Many of my patients come with completely normal evaluation but have no answer for their symptoms. I came across some information that I thought would be interesting.
Many patients report symptoms when consuming gluten, but are negative for serum markers of celiac disease. This so-called non-celiac gluten sensitivity has been maligned in mainstream medicine for years, but new studies point to the potential mechanisms for this effect.
A recent study investigated immune responses in 80 individuals with non-celiac wheat sensitivity who reported gastrointestinal symptoms after consuming wheat products. The control groups consisted of healthy controls as well as individuals with diagnosed celiac disease. All participants adhered to a wheat-, barley-, and rye-free diet for 6 months. Reintroduction of wheat products led to relapse and measurable increase in symptoms.
The key finding was in the serum samples. The researchers discovered changes in biomarkers for the non-celiac wheat-sensitive group. When these participants consumed a diet including wheat, IgG, IgA, and IgM antibodies were significantly higher than in the healthy control group. On the other hand, IgA reactivity was lower than in the celiac group. Serum levels of markers for systemic immune response (LBP- lipopolysaccharide binding protein-and sCD14 measurements) were significantly higher in the non-celiac wheat-sensitive group than in either the healthy or celiac groups. This systemic immune activation correlated with intestinal epithelial damage (measured with FABP2) in both the non-celiac wheat-sensitive group and the celiac group.1
The study also tested serum samples after wheat, barley, and rye were eliminated from the diet. After 6 months of the restricted diet, all participants had significantly improved biomarkers. IgG, IgA, and IgM anti-gliadin antibodies were reduced, as well as LBP, sCD15, EndoCAb IgM, and anti-flagellin IgG and IgM antibodies. Patients’ self-reported symptoms also declined significantly. The systemic immune activation went down as well, paralleling the decrease in reported symptoms.
Importantly, non-celiac wheat-sensitive patients did not show the typical celiac biomarker profile. They did not have elevated antibody responses to TG2 or deamidated gliadin sequences. Duodenal biopsies did not reveal villous atrophy or mucosal abnormalities. However, non-celiac wheat-sensitive participants did have measurable intestinal barrier defects and systemic immune activation.
Another recent study provided further evidence that reintroducing gluten can lead to symptoms in subsets of patients without celiac disease. A double-blind, placebo-controlled trial with 18 patients tested gluten or placebo added to participants’ regular, gluten-free diet. All participants had lymphocytic enteritis without celiac serum markers, but were positive for HLA-DQ2/8, a significant risk factor for celiac disease. More than 90% of the group who received the gluten challenge relapsed and had to stop the study early; 28.5% of the placebo group relapsed. The relapses in the placebo group were likely due to the nocebo effect. These findings suggest that some patients have non-celiac reactions to gluten and lot of associated symptoms. For other patients, non-gluten components of wheat may be responsible for triggering symptoms in non-celiac gluten sensitivity.
Systemic immune activation due to food sensitivities is an area of growing concern for patients. As research continues to substantiate the harmful physical effects of food reactions, the personalized diets used by Functional Medicine practitioners will become increasingly important for good patient outcomes.
From Institute for Functional Medicine