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Intraepithelial Lymphocyte Cytometric Pattern Is a Useful Diagnostic Tool for Coeliac Disease Diagnosis Irrespective of Degree of Mucosal Damage and Age-A Validation Cohort.

ABSTRACT: The study of intraepithelial lymphocytes (IEL) by flow cytometry is a useful tool in the diagnosis of coeliac disease (CD). Previous data showed that an increase in %TCRγδ+ and decrease of %CD3- IEL constitute a typical CD cytometric pattern with a specificity of 100%. However, there are no data regarding whether there are differences in the %TCRγδ+ related to sex, age, titers of serology, and degree of histological lesion. To confirm the high diagnostic accuracy of the coeliac cytometric patterns. To determine if there are differences between sex, age, serology titers, and histological lesion grade. We selected all patients who fulfilled "4 of 5" rule for CD diagnosis (n = 169). There were no differences in %TCRγδ+ between sexes (p = 0.909), age groups (p = 0.986), serology titers (p = 0.53) and histological lesion grades (p = 0.41). The diagnostic accuracy of complete CD cytometric pattern was: specificity 100%, sensitivity 82%, PPV 100%, NPV 47%. We confirmed, in a validation cohort, the high diagnostic accuracy of complete CD pattern irrespective of sex, age, serology titers, and grade of mucosal lesion.

SUBMITTER: Ruiz-Ramirez P

PROVIDER: S-EPMC8155844 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Intraepithelial Lymphocyte Cytometric Pattern Is a Useful Diagnostic Tool for Coeliac Disease Diagnosis Irrespective of Degree of Mucosal Damage and Age-A Validation Cohort.

Ruiz-Ramírez Pablo P Carreras Gerard G Fajardo Ingrid I Tristán Eva E Carrasco Anna A Salvador Isabel I Zabana Yamile Y Andújar Xavier X Ferrer Carme C Horta Diana D Loras Carme C García-Puig Roger R Fernández-Bañares Fernando F Esteve Maria M

Nutrients 20210515 5

<h4>Introduction</h4>The study of intraepithelial lymphocytes (IEL) by flow cytometry is a useful tool in the diagnosis of coeliac disease (CD). Previous data showed that an increase in %TCRγδ<sup>+</sup> and decrease of %CD3<sup>-</sup> IEL constitute a typical CD cytometric pattern with a specificity of 100%. However, there are no data regarding whether there are differences in the %TCRγδ<sup>+</sup> related to sex, age, titers of serology, and degree of histological lesion.<h4>Study aims</h4> ...[more]

PMID: 34063411

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Project description:BackgroundIn sepsis, intestinal barrier dysfunction is often caused by the uncontrolled death of intestinal epithelial cells (IECs). CD4CD8αα intraepithelial lymphocytes (IELs), a subtype of CD4+ T cells residing within the intestinal epithelium, exert cytotoxicity by producing granzyme B (GrB) and perforin (Prf). Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently identified alarmin which stimulates TLR4 on immune cells to induce proinflammatory responses. Here, we hypothesized that eCIRP enhances CD4CD8αα IEL cytotoxicity and induces IEC death in sepsis.MethodsWe subjected wild-type (WT) and CIRP-/- mice to sepsis by cecal ligation and puncture (CLP) and collected the small intestines to isolate IELs. The expression of GrB and Prf in CD4CD8αα IELs was assessed by flow cytometry. IELs isolated from WT and TLR4-/- mice were challenged with recombinant mouse CIRP (eCIRP) and assessed the expression of GrB and Prf in CD4CD8αα by flow cytometry. Organoid-derived IECs were co-cultured with eCIRP-treated CD4CD8αα cells in the presence/absence of GrB and Prf inhibitors and assessed IEC death by flow cytometry.ResultsWe found a significant increase in the expression of GrB and Prf in CD4CD8αα IELs of septic mice compared to sham mice. We found that GrB and Prf levels in CD4CD8αα IELs were increased in the small intestines of WT septic mice, while CD4CD8αα IELs of CIRP-/- mice did not show an increase in those cytotoxic granules after sepsis. We found that eCIRP upregulated GrB and Prf in CD4CD8αα IELs isolated from WT mice but not from TLR4-/- mice. Furthermore, we also revealed that eCIRP-treated CD4CD8αα cells induced organoid-derived IEC death, which was mitigated by GrB and Prf inhibitors. Finally, histological analysis of septic mice revealed that CIRP-/- mice were protected from tissue injury and cell death in the small intestines compared to WT mice.ConclusionIn sepsis, the cytotoxicity initiated by the eCIRP/TLR4 axis in CD4CD8αα IELs is associated with intestinal epithelial cell (IEC) death, which could lead to gut injury.

Dataset Information

Intraepithelial Lymphocyte Cytometric Pattern Is a Useful Diagnostic Tool for Coeliac Disease Diagnosis Irrespective of Degree of Mucosal Damage and Age-A Validation Cohort.

Publications

Intraepithelial Lymphocyte Cytometric Pattern Is a Useful Diagnostic Tool for Coeliac Disease Diagnosis Irrespective of Degree of Mucosal Damage and Age-A Validation Cohort.

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