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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.
Gluten sensitivity is now an everyday term, but exactly what is meant by these two words varies substantially. Nonceliac gluten sensitivity is broadly defined as a symptomatic, morphologic, or immunologic response to the ingestion of gluten-containing foods in individuals in whom celiac disease and wheat allergy have been excluded. However, other products found in gluten-containing grains such as wheat starch and wheat amylase trypsin inhibitors may also play a role in symptom generation and the reported pathophysiologic abnormalities associated with so-called NCGS. In the past decade a variety of potential mechanisms of pathogenesis of NCGS and associated laboratory abnormalities have been described. These range from elevated serum levels of antigliadin IgG to changes in the mucosa (enhanced permeability, changes in the microvillus border), increased and/or activated inflammatory cells (basophils, eosinophils, intraepithelial lymphocytes), increased cytokines (interleukin-8, interferon-gamma), elevated toll-like receptor 2,IgA deposits, and an increase in secreted antibodies directed against gliadin.
These findings are not consistently demonstrated from study to study, which likely reflects the difficulty in defining NCGS and the heterogeneity of the condition. Since no proven mechanism or established diagnostic criteria for the disorder of NCGS exist, it is likely that the patients being studied in each report represent divergent populations. In essence, the studies can only differentiate subjects with celiac disease, wheat allergy, and true healthy controls, leaving patients with NCGS and other food sensitivities, intestinal bacterial overgrowth, and/or functional GI disorders as a rather ill-defined cohort.
The study by Dr. Bucci and colleagues aims to evaluate the immunologic response to a gliadin challenge in duodenal mucosa in patients with NCGS compared with responses in patients with CD and healthy controls. All 69 subjects with CD (treated or newly diagnosed) exhibited duodenal activation after in vitro gliadin stimulation while no significant responses were observed with gliadin challenge in duodenal mucosa from 16 NCGS subjects. This study adds to the body of literature that demonstrates differences between CD and NCGS with the goal of better defining NCGS and understanding the underlying mechanisms, but much more research is needed to advance the field.
Dr. Sheila Crowe is a professor of medicine and director of research in the division of gastroenterology at the University of California at San Diego. She said she had no relevant financial disclosures.
Gluten sensitivity is now an everyday term, but exactly what is meant by these two words varies substantially. Nonceliac gluten sensitivity is broadly defined as a symptomatic, morphologic, or immunologic response to the ingestion of gluten-containing foods in individuals in whom celiac disease and wheat allergy have been excluded. However, other products found in gluten-containing grains such as wheat starch and wheat amylase trypsin inhibitors may also play a role in symptom generation and the reported pathophysiologic abnormalities associated with so-called NCGS. In the past decade a variety of potential mechanisms of pathogenesis of NCGS and associated laboratory abnormalities have been described. These range from elevated serum levels of antigliadin IgG to changes in the mucosa (enhanced permeability, changes in the microvillus border), increased and/or activated inflammatory cells (basophils, eosinophils, intraepithelial lymphocytes), increased cytokines (interleukin-8, interferon-gamma), elevated toll-like receptor 2,IgA deposits, and an increase in secreted antibodies directed against gliadin.
These findings are not consistently demonstrated from study to study, which likely reflects the difficulty in defining NCGS and the heterogeneity of the condition. Since no proven mechanism or established diagnostic criteria for the disorder of NCGS exist, it is likely that the patients being studied in each report represent divergent populations. In essence, the studies can only differentiate subjects with celiac disease, wheat allergy, and true healthy controls, leaving patients with NCGS and other food sensitivities, intestinal bacterial overgrowth, and/or functional GI disorders as a rather ill-defined cohort.
The study by Dr. Bucci and colleagues aims to evaluate the immunologic response to a gliadin challenge in duodenal mucosa in patients with NCGS compared with responses in patients with CD and healthy controls. All 69 subjects with CD (treated or newly diagnosed) exhibited duodenal activation after in vitro gliadin stimulation while no significant responses were observed with gliadin challenge in duodenal mucosa from 16 NCGS subjects. This study adds to the body of literature that demonstrates differences between CD and NCGS with the goal of better defining NCGS and understanding the underlying mechanisms, but much more research is needed to advance the field.
Dr. Sheila Crowe is a professor of medicine and director of research in the division of gastroenterology at the University of California at San Diego. She said she had no relevant financial disclosures.
Gluten sensitivity is now an everyday term, but exactly what is meant by these two words varies substantially. Nonceliac gluten sensitivity is broadly defined as a symptomatic, morphologic, or immunologic response to the ingestion of gluten-containing foods in individuals in whom celiac disease and wheat allergy have been excluded. However, other products found in gluten-containing grains such as wheat starch and wheat amylase trypsin inhibitors may also play a role in symptom generation and the reported pathophysiologic abnormalities associated with so-called NCGS. In the past decade a variety of potential mechanisms of pathogenesis of NCGS and associated laboratory abnormalities have been described. These range from elevated serum levels of antigliadin IgG to changes in the mucosa (enhanced permeability, changes in the microvillus border), increased and/or activated inflammatory cells (basophils, eosinophils, intraepithelial lymphocytes), increased cytokines (interleukin-8, interferon-gamma), elevated toll-like receptor 2,IgA deposits, and an increase in secreted antibodies directed against gliadin.
These findings are not consistently demonstrated from study to study, which likely reflects the difficulty in defining NCGS and the heterogeneity of the condition. Since no proven mechanism or established diagnostic criteria for the disorder of NCGS exist, it is likely that the patients being studied in each report represent divergent populations. In essence, the studies can only differentiate subjects with celiac disease, wheat allergy, and true healthy controls, leaving patients with NCGS and other food sensitivities, intestinal bacterial overgrowth, and/or functional GI disorders as a rather ill-defined cohort.
The study by Dr. Bucci and colleagues aims to evaluate the immunologic response to a gliadin challenge in duodenal mucosa in patients with NCGS compared with responses in patients with CD and healthy controls. All 69 subjects with CD (treated or newly diagnosed) exhibited duodenal activation after in vitro gliadin stimulation while no significant responses were observed with gliadin challenge in duodenal mucosa from 16 NCGS subjects. This study adds to the body of literature that demonstrates differences between CD and NCGS with the goal of better defining NCGS and understanding the underlying mechanisms, but much more research is needed to advance the field.
Dr. Sheila Crowe is a professor of medicine and director of research in the division of gastroenterology at the University of California at San Diego. She said she had no relevant financial disclosures.
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.
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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major finding: Challenging duodenal biopsy specimens with gliadin in gluten-sensitive patients without celiac disease is nondiagnostic for this condition.
Data source: A blinded study of the serology and histology of 119 patients with and without gluten sensitivity.
Disclosures: The authors disclosed no financial conflicts. They wrote that the study was funded by the regional public health department.