Dataset Information

Activated gut-homing CD8⁺ T cells for coeliac disease diagnosis on a gluten-free diet.

ABSTRACT:

Background

The diagnosis of coeliac disease (CD) in individuals that have started a gluten-free diet (GFD) without an adequate previous diagnostic work-out is a challenge. Several immunological assays such as IFN-γ ELISPOT have been developed to avoid the need of prolonged gluten challenge to induce the intestinal damage. We aimed to evaluate the diagnostic accuracy of activated gut-homing CD8⁺ and TCRγδ⁺ T cells in blood after a 3-day gluten challenge and to compare it with the performance of IFN-γ ELISPOT in a HLA-DQ2.5 subsample.

Methods

A total of 22 CD patients and 48 non-CD subjects, all of them following a GFD, underwent a 3-day 10-g gluten challenge. The percentage of two T cell subsets (CD8⁺ CD103⁺ β7^hi CD38⁺/total CD8⁺ and TCRγδ⁺ CD103⁺ β7^hi CD38⁺/total TCRγδ⁺) in fresh peripheral blood drawn baseline and 6 days after the challenge was determined by flow cytometry. IFN-γ ELISPOT assays were also performed in HLA-DQ2.5 participants. ROC curve analysis was used to assess the diagnostic performance of the CD8⁺ T cell response and IFN-γ ELISPOT.

Results

Significant differences between the percentage of the two studied subsets of CD8⁺ and TCRγδ⁺ cells at days 0 and 6 were found only when considering CD patients (p < 10^-3 vs. non-CD subjects). Measuring activated CD8⁺ T cells provided accurate CD diagnosis with 95% specificity and 97% sensitivity, offering similar results than IFN-γ ELISPOT.

Conclusions

The results provide a highly accurate blood test for CD diagnosis in patients on a GFD of easy implementation in daily clinical practice.

SUBMITTER: Fernandez-Banares F

PROVIDER: S-EPMC8493675 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS.We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years.Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%).The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms.

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