TNF-α, IL-17 AND IL-22 PRODUCTION IN THE RECTAL MUCOSA OF NON-CELIAC WHEAT SENSITIVITY PATIENTS: ROLE OF ADAPTIVE IMMUNITY

Abstract

In recent years, a new gluten- or wheat-related disease has emerged, a condition labelled "non-celiac gluten sensitivity" (NCGS) or "non-celiac wheat sensitivity" (NCWS). NCWS pathogenesis is still uncertain and attributed to very different mechanisms. We aimed to study the different T lymphocyte subsets in the rectal mucosa of NCWS patients, to demonstrate the possible contribution of adaptative immune response. Twelve patients (11 females, 1 male, age range 23-61 years, median 32) with a definitive diagnosis of NCWS were recruited at random for the present study. They underwent rectal endoscopy with multiple mucosal biopsies at the end of a double-blind placebo-controlled (DBPC) wheat challenge when they reported the reappearance of the symptoms. As controls we included 11 "healthy patients", sex- and age-matched with the patients, who underwent colonoscopy evaluation for rectal bleeding due to hemorrhoids. Cells freshly obtained from rectal tissue were stained to detect anti-CD45, anti-CD3, anti-CD4, and anti-CD8. Furthermore, intracellular staining was performed with anti-Tumor Necrosis Factor (TNF)-α, anti-interleukin (IL)-17, and anti-IL-22. Production of TNF-α by CD45+, CD3+, CD4+ and CD8+ cells, as well as of IL-17 by CD4+ cells, was higher in the rectal tissue of NCWS patients than in controls. On the contrary, IL-22 production by CD8+ cells was lower in NCWS patients than in the controls. In NCWS patients diagnosed by DBPC wheat challenge, there is a complex immunological activation, with a significant role for the adaptive response.