Clinical study distinguishes between gluten-sensitivity and celiac disease
By: Peter on April 25, 2011
Celiac disease has been the subject of extensive scientific research, but work on gluten-sensitivity is only just starting to catch up. In a collaborative study between four laboratories in Italy and the US, an attempt was made to separate these two conditions [Ref. 1]. The actual article is rather indigestible (!), but I will try to summarize the key points of interest to a general audience. This was a large study, consisting of 22 patients with gluten-sensitivity, 42 with celiac disease, and 39 control subjects. All patients were subjected to a gluten-challenge for four months, followed by a gluten-free diet. While the terms gluten-intolerance and gluten-sensitivity are used differently by different people, the authors set strict criteria for selecting the patients with “gluten-sensitivity”. These were defined as meeting three criteria: a) little or no intestinal damage after the gluten-challenge (Marsh stage 0 or 1), b) negative for anti-endomysium or anti-tissue-tranglutaminase antibodies in the blood, and c) their symptoms improved on a gluten-free diet.
HLA DQ2/DQ8 genetics and anti-gliadin antibody status are different for gluten-sensitivity versus celiac disease
The presence of the HLA genes DQ2 or DQ8 is characteristic for almost all celiac patients [Ref. 2]. In contrast, in this study, only 43% of the gluten-sensitive patients were DQ2/DQ8 positive, which is similar to that of the general population.
The presence of anti-gliadin antibody in the blood is a common (though not definitive) phenomenon for celiac patients. In this study, only 43% of patients were antibody-positive. This implies that anti-gluten antibody is not a good marker for gluten-sensitivity. Interestingly, a substantial fraction (44%) of the antibody-positive patients lacked DQ2/DQ8, another difference from celiac patients.
No “leaky-gut” in gluten-sensitive patients
Celiac disease is often accompanied by an increase in gut permeability [Ref. 3] (referred to by some as “leaky-gut”, a term that has unfortunately been picked up by the popular media). In contrast, this study showed that gluten-sensitive patients actually had less gut permeability than control subjects.
None of the gluten-sensitive patients had IgE anti-wheat antibodies—the response to gluten is quite different from an allergic reaction to wheat.
Innate versus adaptive immune system
The results support the idea that in gluten-sensitive patients, gluten activates the “innate” immune system; in other words, the protein is immediately recognized as foreign or toxic. Celiac disease, in contrast, involves the activation of the “adaptive” immune system, followed by an accidental (autoimmune) reaction to tissue transglutaminase.
- Gluten-sensitivity in the absence of celiac disease is a real phenomenon, and can be clearly distinguished at a molecular level.
- Negative HLA typing for DRQ2/DRQ8 doesn’t rule out the presence of gluten-sensitivity.
- Negative anti-gliadin antibody tests don’t rule out the presence of gluten-sensitivity.
- Gluten-free diet resulted in a relief from symptoms in gluten-sensitive patients within a few days, and this lasted for the whole 4 years of the study.
- Physicians have little to rely on for a diagnosis, other than the reduction in gastrointestinal symptoms following a gluten-free diet.
- Gluten-sensitive patients do not have “leaky-gut”.
Clearly, this is an exciting field of research, especially since the prevalence of gluten-sensitivity is estimated to be perhaps 6% of the general population [Ref. 4]—six-fold more common than celiac disease.
Finally, this kind of study may be difficult to repeat, since it involves deliberately subjecting known celiac patients to a further gluten-challenge, but with no obvious clinical benefit to the patient. These people are to be commended for their generosity for the sake of science.
Ref. 1: Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011; 9: 23 doi:10.1186/1741-7015-9-23 Sapone, A., Lammers, KM., et al.
Ref. 3: Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut 1993 Mar;34(3):354-7. van Elburg, RM., Uil, JJ., et al.