The Predictive Value of Serum Cytokines for Distinguishing Celiac Disease from Non-Celiac Gluten Sensitivity and Healthy Subjects

Abstract

Background: It has been established that the level of some inflammatory cytokines increases in CD and NCGS in comparison with healthy subjects. Therefore, the primary interest in our research was proposing an accurate tool to diagnose patients with CD and NCGS from healthy individuals in an Iranian population. Methods: The serum samples were examined in 171 participants, including 110 CD patients, 46 healthy individuals, and 15 NCGS. The commercial ELISA kits were used to detect the level of the following cytokines: IL-1, IL-6, IL-8, IL-15, and IFN-γ. The ROC curve analysis was applied to determine the optimal thresholds for high sensitivity, specificity, positive and negative predictive values of cytokines, as the indicators of CD, NCGS, and healthy control groups. Results: In NCGS group, the values of AUC for IL-1, IL-8, and IFN-γ were 71%, 78%, and 70%, respectively. To differentiate the CD and NCGS groups from the control group, IL-15 had the highest sensitivity (82.70%), specificity (56.50%), positive predictive value (81.98%), and negative predictive value (57.78%), followed by IL-8 with the highest sensitivity of 74.50%, specificity of 73.30%, and positive and negative predictive values of 95.35% and 30.21%, respectively. Conclusion: The obtained results demonstrate that IL-15 and IL-8 could be proposed as potential markers in their optimal cutoff points for distinguishing CD from the NCGS and the healthy control. Based on our findings, the evaluation of cytokine levels can be recommended as a useful tool for the diagnosis of CD and NCGS in a clinical practice.

More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa

“…The inflammatory response was conspicuously higher in CD subjects although pro-inflammatory cytokine- expressing cells were also evident in NCSRWS patients, except for IL-6- and IL-8-expressing cells. These findings have been previously reported by other studies that evaluated cytokine levels on serum and peripheral blood mononuclear cells or duodenal mucosa culture supernatants by ELISA [ 32 – 36 ].…”

“…Since our objective was to determine the cytokine expression in CD and NCSRWS patients we did not consider necessary to evaluate TLRs. It should be noted that our results pertaining IL-6 and IL-8 in NCSRWS patients are similar to those reported in mononuclear cells culture supernatants (ELISA) from NCGS subjects [ 32 ]. On the other hand, we determined the presence of IL-6+ and IL-8+ cells using tissue immunohistochemistry, but we did not determine the individual cellular cytokine production.…”

More fuel to the fire: Some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa.

“…The in ammatory response was conspicuously higher in CD subjects although pro-in ammatory cytokine-expressing cells were also evident in NCSRWS patients, except for IL-6-and IL-8-expressing cells. These ndings have been previously reported by other studies that evaluated cytokine levels on serum and peripheral blood mononuclear cells or duodenal mucosa culture supernatants by ELISA (32)(33)(34)(35)(36).…”

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test

“…In patients with NCGS/WS, a systemic immune activation has been demonstrated; it was documented by increased serum levels of soluble CD14 and LPS-binding protein, as well as antibody reactivity to bacterial LPS and flagellin [ 10 ], enhanced expression of Toll-like receptor 2 (TLR2) [ 5 ], increased antibodies against gluten proteins [ 17 , 47 ], raised interferon gamma, interleukin (IL)-1 beta, IL-2, IL-12, IL-15, transforming growth factor (TNF) beta1, and TNF-α-expressing duodenal cells [ 3 , 29 ], increased serum levels of IL-8 and IL-15 [ 48 ], moderate intra-epithelial infiltration of eosinophils and lymphocytes, with increased inflammatory and regulatory CD4+ cells [ 6 , 13 , 17 , 47 , 49 , 50 ], and a high frequency of associated autoimmune diseases [ 7 , 51 ]. It has been hypothesized that individuals with NCGS/WS with a prevalent pathogenetic role for the FODMAPs, instead of gluten, may be a different patient population with less-prominent immunologic characteristics [ 6 ].…”