I think most of us have met people who have symptoms of celiac disease, but when tested, are told that their celiac antibody blood tests and biopsy results are negative (normal). Some of these people are labeled “gluten intolerant” or “gluten sensitive” by their doctors, others are told they may have “early” celiac disease, or “pre” celiac disease, and the rest are told that they have nothing wrong and are often advised to continue to eat gluten. Many continue to eat gluten and find themselves getting sicker and sicker, with an improvement or disappearance of symptoms when they go gluten-free. Then, when they go gluten-free, since they are “gluten intolerant” as opposed to having celiac disease, it is unclear how closely they need to be followed for vitamin deficiencies, the development of additional autoimmune disorders, and other problems that are associated with long-standing celiac disease.
Whenever I hear that a person is “gluten intolerant” I wonder whether or not the diagnosis of celiac disease was actually missed. Celiac blood antibody testing can be unreliable in infants and toddlers, people who have a condition called serum IgA deficiency (occurs in up to 3% of celiacs), and when patients are tested after they have already started on the gluten-free diet. Likewise, endoscopies and biopsies are often done incorrectly (see link) which can lead to celiac-induced intestinal damage being missed.
I recently read, with much interest, an article called, “Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance,” which was published this month by a group of celiac researchers in Italy. Although it’s a bit technical, I will do my best to summarize it for you.
In this study, the gluten-intolerant subjects consisted of 78 pediatric patients who had symptoms of celiac disease but normal celiac antibodies (anti-TTG, also called TTG IgA) and normal small bowel biopsies. None of the subjects were IgA deficient. Of the 78 gluten intolerant subjects, 12 were found to have anti-TTG antibodies present in the tissue biopsies from their intestines–to clarify, anti-TTG antibodies were found in their intestines, but not in their blood. 3 of the 12 patients in this “gluten intolerant” group, with TTG antibodies localized to the intestine only, were started on a GFD diet and they all had improvement in symptoms and anemia after 24 months on the gluten-free diet. Of the 9 patients with anti-TTG antibodies in the intestines who were continued on a gluten-containing diet, 2 of the 12 had celiac disease at 24 month follow-up. The remaining 7 “gluten intolerant” subjects who remained on gluten-containing diets appeared to have an improvement in symptoms at the 24 month mark, but it is unclear if this reflected a period of remission v. a true resolution of the intestinal antibody response, as there has been no long term follow-up, and as far as I can tell, biopsies were not repeated.
Although this study has a very small sample size, it demonstrates that there are some “gluten intolerant” patients who actually have subclinical celiac disease. In these cases, the celiac immune response is contained to the intestines only and villous atrophy (the hallmark of celiac disease) has not yet occurred. It appears that these individuals benefit from treatment with the gluten free diet.
I am curious to see if the long-term follow-up of the remaining 7 gluten intolerant subjects will be published in the future, and if some of them will also go on the develop celiac disease. I am also curious to see if celiac antibody testing of intestinal biopsy specimens will eventually become part of the standard of care in the clinical investigation of celiac disease.
Quaglia, S, De Leo, L, Ziberna, F, et al. Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance. Cellular and Molecular Immunology advance online publication, 28 April 2014; doi:10.1038/cmi.2014.32.