Subclass Profile of IgG Antibody Response to Gluten Differentiates Non-Celiac Gluten Sensitivity from Celiac Disease

Abstract:

Celiac disease (CD) is an autoimmune enteropathy triggered by exposure to gluten proteins, leading to intestinal inflammation and villous atrophy in genetically predisposed individuals. It is associated with robust B cell and antibody responses to gluten and to the transglutaminase 2 (TG2) autoantigen 1. In contrast, non-celiac gluten sensitivity (NCGS) is a poorly understood clinical entity defined by onset of symptoms in response to ingestion of gluten-containing food without the prerequisite serologic or histologic features of CD 2. There are no established biomarkers yet for NCGS, but recent research points to a biological basis, revealing a state of systemic immune activation in conjunction with a compromised intestinal epithelium 2, 3. We and others have demonstrated a significant increase in IgG antibody to gluten in NCGS at levels similar to CD 2, 3. Accordingly, it has been speculated that an enhanced IgG response to gluten may be a common link between CD and NCGS 2. However, whether and how B cell reactivity to gluten may differ in these conditions, especially in the context of possible relevance to intestinal pathology, have not been examined. In this study, we extend earlier data to show that the anti-gluten IgG antibody in NCGS is significantly different from CD in subclass distribution and in its relationship to intestinal cell damage. The findings are suggestive of a sustained primary B cell response to gluten in CD despite the condition’s chronicity, and a more advanced and tolerogenic immune response to gluten in NCGS.