Background The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal infammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by fow cytometry or frozen section immunohistochemistry (IHC), is a specifc marker for CD. Aim To establish a new IHC assay for γδ-IELs applicable to formalin-fxed parafn-embedded (FFPE) duodenal biopsies. Methods We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis. Results Compared to those in non-celiac controls (n=51), γδ-IEL density was signifcantly increased in newly diagnosed celiac disease patients (n=22, p<0.0001). In ROC-curve analysis, the cutof of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specifcity 95%). γδ-IEL density in CD patients on a gluten-free diet (n=53) were also higher than in controls (p<0.0001), but lower than those in newly diagnosed CD (p<0.0001). The diagnostic value of γδ-IELs outperformed that of CD3+IELs in both patient groups. γδ-IELs were better than CD3+IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n=12). Conclusions Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specifcity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.

Correction to: a new intraepithelial  T-Lymphocyte marker for celiac disease classification in formaline-fixed paraffine-embedded (FFPPE) duodenal biopsies

C. Lamacchia;
2020-01-01

Abstract

Background The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal infammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by fow cytometry or frozen section immunohistochemistry (IHC), is a specifc marker for CD. Aim To establish a new IHC assay for γδ-IELs applicable to formalin-fxed parafn-embedded (FFPE) duodenal biopsies. Methods We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis. Results Compared to those in non-celiac controls (n=51), γδ-IEL density was signifcantly increased in newly diagnosed celiac disease patients (n=22, p<0.0001). In ROC-curve analysis, the cutof of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specifcity 95%). γδ-IEL density in CD patients on a gluten-free diet (n=53) were also higher than in controls (p<0.0001), but lower than those in newly diagnosed CD (p<0.0001). The diagnostic value of γδ-IELs outperformed that of CD3+IELs in both patient groups. γδ-IELs were better than CD3+IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n=12). Conclusions Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specifcity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/394496
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