Celiac disease-associated serum antibodies and the expression of the human leukocyte antigen complex (HLA) DQ2 genotype can identify individuals with diarrhea-dominant irritable bowel syndrome (IBS-D) who are likely to respond to a gluten-free diet, investigators reported in an article appearing in the July issue of Clinical Gastroenterology and Hepatology.
Although the presence of villous atrophy in the small intestine together with gluten sensitivity are the typical diagnostic criteria for classical celiac disease in patients with diarrhea, gluten sensitivity may also cause abdominal symptoms in the absence of villous atrophy, wrote Dr. Ulrich Wahnschaffe of Ernst-Moritz-Arndt Universität, Greifswald (Germany) and his colleagues.
In a previous study, the investigators found that a subgroup of patients with IBS-D without villous atrophy benefitted from a gluten-free diet; the patients were identified by the expression of HLA-DQ2 (A1*0501/B1*0201) and increased antibodies against gliadin and/or tissue-transglutaminase in duodenal aspirate.
The investigators in the current study sought to determine whether these serum antibodies, in association with HLA-DQ2 expression, are markers for gluten sensitivity. They measured HLA-DQ2 expression and celiac disease-associated IgA and IgG serum antibodies against gliadin and tissue-transglutaminase in 145 patients with IBS-D, 74 celiac patients (30 untreated and 44 treated), 57 patients with active inflammatory bowel disease (IBD) who were used as the disease control group, and 62 healthy controls.
Each patient underwent abdominal ultrasound, upper and lower endoscopy, distal duodenal biopsies, and blood and stool tests.
Of the IBS-D patients, 41 participated in a nonrandomized evaluation of a gluten-free diet for 6 months. Follow-up antibody levels, stool frequency, and gastrointestinal symptom scores were collected for these patients.
Expression of HLA-DQ2 was observed in all of the patients with untreated celiac disease, 93% of those with treated celiac disease, and 39% of the IBS-D patients. “HLA-DQ2 expression was significantly more frequent in IBS-D patients, compared [with IBD] patients and controls,” the authors wrote.
IgA antibodies against gliadin and/or tissue-transglutaminase were observed in 93% of the untreated celiac disease group, 7% of those with treated celiac disease, 2% of those with IBS-D, and no patients with IBD, confirming the significance of these IgA antibodies as a marker for active celiac disease.
In contrast, “increased serum IgG against gliadin and/or tissue transglutaminase were present not only in most patients with untreated [celiac disease], but also in the majority of patients with treated celiac disease and may therefore represent markers for gluten sensitivity,” the authors wrote.
About one-third of the IBS-D patients were positive for this marker, and the proportion of patients with the marker was significantly higher in IBS-D than in IBD patients.
In the extended gluten-free diet study, those IBS-D patients who were HLA-DQ2 positive had significant improvement in diarrhea in response to the diet. In addition, “a symptom score covering typical gastrointestinal symptoms of IBS, … like abdominal pain or bloating, improved to normal values in most patients expressing HLA-DQ2 or with celiac disease-associated serum IgG antibodies after gluten-free diet,” they wrote, noting that this association supports the presence of gluten sensitivity in a subgroup of approximately 17% of IBS-D patients.
The investigators determined that expression of HLA-DQ2 in combination with serum IgG against gliadin and/or tissue-transglutaminase was a predictor of response to a gluten-free diet in IBS-D patients.
“Sensitivity to predict the response to gluten-free diet was higher for HLA-Dq2 expression, whereas specificity was higher for celiac disease-associated IgG; both parameters combined yielded positive and negative predictive values of 56% and 88%, respectively,” they wrote.
These values, although not ideal, are acceptable, because the gluten-free diet is a nontoxic, relatively inexpensive treatment option, they added.
“Our findings, which require confirmation by randomized studies, suggest that screening for HLA-DQ2 and/or celiac disease-associated IgG [in patients with IBS-D] could identify an additional larger subgroup of patients without villous atrophy or celiac disease-associated IgA who will benefit from gluten-free diet,” the authors concluded.