The in vitro gliadin challenge is not useful in diagnosing nonceliac gluten sensitivity, reported Dr. Cristina Bucci and her colleagues in the October issue of Clinical Gastroenterology and Hepatology.
"Even if a clinical form of gluten intolerance other than celiac disease [CD] seems to be recognized both by patients and clinicians, there is no clear evidence of a mucosal or serologic modification that can be used as stigmata of the disease in those individuals," the authors wrote.
Dr. Bucci of the University of Salerno (Italy) and her colleagues looked at 119 adult patients who were negative for wheat allergy by a skin prick test.
They were divided into four cohorts.
The first cohort was the nonceliac gluten-sensitive (NCGS) group, who had negative serology and histology for CD but reported irritable bowel symptoms after ingesting gluten (n = 16).
The second group comprised untreated celiac patients at the moment of diagnosis, who had not been on a gluten-free diet (n = 35).
The third group included treated celiac patients on a gluten-free diet (n = 34), and the fourth group was made up of healthy controls who were being worked up for reasons other than suspicion of CD (n = 34).
All participants underwent upper endoscopy for duodenal biopsies, and the investigators also assessed patients’ serum anti–tissue transglutaminase antibodies, antiendomysium antibodies, and total IgA, plus human leukocyte antigen (HLA), where appropriate.
Next, the researchers assembled duodenal biopsy specimens from each patient, and a blinded biologist challenged these specimens to a gliadin digest (1 mg/mL).
They then assessed both early markers of inflammation in these specimens, including PY99 (antiphosphotyrosine monoclonal antibody), HLA-DR (the major histocompatibility complex, class II, DR), as well as later markers, like CD3 (a marker of mature T lymphocytes), CD25 (the inducible interleukin-2 receptor in both lymphoid and myeloid cells), and CD69 (a marker of T-cell activation).
Two biopsy specimens from each patient were left untouched by gliadin, for comparison.
The authors found that the specimens from all CD patients, regardless of current diet, showed increased immunofluorescence intensity when stimulated with gliadin, both for early and late inflammation markers.
On the other hand, reported Dr. Bucci, "only three healthy controls and three NCGS patients showed a weak, inconsistent response to the gliadin challenge for some, but not all, inflammation markers, and the mucosa of the majority of them did not seem to be activated by those stimuli."
Furthermore, one of these NCGS patients and one control were positive for Helicobacter pylori.
In addition, the authors wrote that tissue transglutaminase deposits were present at variable intensity in CD patients, but were not seen in NCGS patients and healthy controls.
According to Dr. Bucci, "A few years ago, only one type of gluten intolerance, CD and its skin form, dermatitis herpetiformis, was recognized by the scientific community."
Now that clinical practice has identified gluten-sensitive individuals who are not celiac positive, however, "wheat components other than proteins, for example, carbohydrates that already had been associated with the appearance of gastrointestinal symptoms in patients with IBS, also should be investigated for their role in the pathogenesis of NCGS."
The authors disclosed no financial conflicts. They wrote that the study was funded by the regional public health department.
