Evidence map›Paper›PMID 33140183›Full record

ArticleDigestive diseases and sciences2021

A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies.

Alina Popp, Juha Taavela, Paolo Graziano, Paola Parente, Claudia Covelli, Carmela Lamacchia, Angelo Andriulli, Markku Mäki, Jorma Isola

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Digestive diseases and sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

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  4. T cell receptors for antigen on intraepithelial cytolytic T lymphocytes in celiac disease engage enterocyte HLA-E and HLA-B.Proceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Alina PoppFaculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
Juha TaavelaFaculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
Paolo GrazianoPathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Paola ParentePathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Claudia CovelliPathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Carmela LamacchiaDepartment of the Science of Agriculture, Food and Environment, University of Foggia, Foggia, Italy.
Angelo AndriulliPathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Markku MäkiFaculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
Jorma IsolaFaculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland. jorma.isola@tuni.fi.ORCID 0000-0002-0849-5939
Casa Sollievo della Sofferenza · ITTampere University Hospital · FICarol Davila University of Medicine and Pharmacy · ROUniversity of Foggia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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 inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD.

aimTo establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies.

methodsWe 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.

resultsCompared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 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).

conclusionsIntraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity 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.

Indexed as

FormaldehydeParaffin EmbeddingTissue FixationAntibodies, MonoclonalBiomarkersCeliac DiseaseDuodenumImmunohistochemistryReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesAntibodies, MonoclonalBiomarkersFormaldehydeReceptors, Antigen, T-Cell, gamma-deltaAutoimmuneCeliac diseaseDiagnosticsHistopathologyInflammationLymphocyteSmall bowel

Identifiers

PMID33140183
PMCPMC8449760
OpenAlexW3096899727

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.