Non-Celiac Wheat Sensitivity as an Allergic Condition: Personal Experience and Narrative Review

Abstract

OBJECTIVES:Non-celiac wheat sensitivity (NCWS) is a newly described clinical entity characterized by symptoms, which can involve the gastrointestinal tract, the nervous system, the skin, and other organs. There is little data on the pathogenesis of NCWS and it is probable that different pathogenic mechanisms are involved in the different clinical manifestations of the disease. The only common denominator of NCWS " syndrome " is wheat consumption: the symptoms disappear on exclusion of wheat from the diet, and reappear on wheat consumption. The objective of this study was to review our prior data regarding NCWS and to review relevant medical literature regarding NCWS, with particular attention to the hypothesis that NCWS patients could suffer from non-immunoglobulin E (IgE)-mediated wheat allergy. METHODS:We reviewed our data on 276 patients diagnosed with NCWS by means of double-blind placebocontrolled (DBPC) wheat challenge. The data indicating a possible wheat allergy diagnosis were examined and other data in the literature were reviewed; we review the role of serum immunoglobulin G antibodies and the basophil activation assay in food allergy, and the histology fi ndings in the food allergy diagnosis. RESULTS:The comparison between patients suffering from NCWS and presenting with irritable bowel syndrome (IBS) and controls with IBS not due to NCWS showed that NCWS was characterized by: a personal history of food allergy in the pediatric age (0.01), coexistent atopic diseases (0.0001), positive serum anti-gliadin (0.0001) and anti-betalactoglobulin (0.001) antibodies, positive cytofl uorimetric assay revealing in vitro basophil activation by food antigens (0.0001), and a presence of eosinophils in the intestinal mucosa biopsies (0.0001).CONCLUSIONS: Patients with NCWS and multiple food sensitivity show several clinical, laboratory, and histological characteristics that suggest they might be suffering from non-IgE-mediated food allergy. However, other pathogenic mechanisms need to be considered.

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up

“…We studied a cohort of patients who had a marked immunologic component, which can suggest an allergic condition. 10 It could be hypothesized that these patients were suffering from a non-IgE-mediated food allergy, a hypothesis that may be consistent with the confocal endoscopy images of the duodenal mucosa during provocative tests in IBS patients. 11 Furthermore, the study was underpowered to determine if male sex was associated with adherence to the GFD.…”

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies

“…In addition, in this respect, we and others have suggested that NCWS cannot be considered a unique condition, but rather an "umbrella" term that includes various conditions with different types of pathogenesis. 12,[29][30][31][32][33] Regarding our previous hypothesis that NCWS could be an allergic disease, 28 it should also be remembered that negative IgE test results cannot exclude food allergy. In the absence of specific biomarkers, we should cautiously indicate that this high frequency of autoimmunity can apply to NCWS patients who react to a challenge with a low amount of wheat (equivalent to about 20 g bread in our experiment).…”

Other Dietary Confounders: FODMAPS et al.

“…The principal evidence that gluten causes those effects has comprised the reported response to a gluten-free diet and re-challenge with wheat [5,6,7]. Gluten-specific immunological effects, notably the production of circulating antibodies to gluten components, have also had significance attached to them despite their poor sensitivity and specificity in coeliac disease [8,9]. Only coeliac disease, dermatitis herpetiformis and ataxia syndromes have a reasonable to high level of evidence in their immunological response and pathophysiology.…”

“…Furthermore, the effects of wheat/gluten are clearly heterogeneous with several pathogenic pathways involving or independent of inflammation likely. This is best illustrated by the range of events from wheat allergy syndromes [15] to coeliac disease [16] to wheat sensitivity with eosinophilic gut infiltration [9] to gluten-induced feeling of depression where no markers of inflammation or gluten-related immune phenomena exist [10]. …”

“…Some groups have confined their work to those without evidence of abnormal immune responses or injury to the gut [11,12] characterised by inflammation and mucosal structural changes, while others have examined mixed groups with a proportion having evidence of mucosal injury or abnormalities [5,9,13]. The problem with having evidence of immune activation to gluten is that it is not easy to exclude coeliac disease or coeliac-specific immune events such as specific T-cell sensitivity to ‘toxic' gluten peptides [14].…”