Autoantibodies Toward ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase Are Reliable Serological Pre-endoscopic Markers of Corpus Atrophic Gastritis.


Journal

Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142

Informations de publication

Date de publication:
10 2020
Historique:
entrez: 8 10 2020
pubmed: 9 10 2020
medline: 17 7 2021
Statut: ppublish

Résumé

Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and Helicobacter pylori antibodies. Parietal cell autoantibodies (PCAs) against the gastric proton pump (ATP4) are potential serological biomarkers of CAG. The purpose of this study was to compare the diagnostic performance of PCA and pepsinogen I tests in patients with clinical suspicion of CAG with the histopathological evaluation of gastric biopsies as reference standard. A prospective case-finding study was performed on 218 naive adult patients (131 women, median age 65 years) who underwent gastric biopsies to confirm/exclude CAG. Patients with histopathological CAG were defined as cases, conversely as controls. Autoantibodies against the individual alpha (ATP4A) and beta (ATP4B) subunits of ATP4 were measured by luciferase immunoprecipitation, and global PCA and pepsinogen I by enzyme-linked immunosorbent assay. Histopathology classified 107 subjects (49%) as cases (CAG+, autoimmune 81.2%, and multifocal extensive 18.8%) and 111 subjects (51%) as controls (CAG-). In cases, ATP4A, ATP4B, and PCA titers were increased compared with controls, whereas pepsinogen I was reduced (P < 0.0001 for all). ATP4B, ATP4A, and pepsinogen I tests showed sensitivities of 77%, 75%, and 73% and specificities of 88%, 88%, and 80%, respectively. The receiver operating characteristic (ROC) area under the ROC curve (AUC) of these serological biomarkers confirmed their ability to discriminate cases from controls (ATP4B = 0.838, ATP4A = 0.826, pepsinogen I = 0.775, and PCA = 0.805), whereas the partial ROC-pAUC90 analysis showed that the ATP4B test had the best diagnostic performance (P = 0.008 vs ATP4; P = 0.0002 vs pepsinogen I). The presence of autoimmune or extensive gastritis was not significantly different between ATP4B positive or negative cases (P = 0.217). PCAs are promising serological biomarkers for the identification of CAG in high-risk individuals, particularly in an autoimmune pattern but also in an extensive-multifocal atrophy pattern.

Identifiants

pubmed: 33031196
doi: 10.14309/ctg.0000000000000240
pii: 01720094-202010000-00004
pmc: PMC7544173
doi:

Substances chimiques

Autoantibodies 0
Biomarkers 0
Pepsinogen A 9001-10-9
ATP4A protein, human EC 3.6.3.10
H(+)-K(+)-Exchanging ATPase EC 3.6.3.10

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e00240

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Auteurs

Edith Lahner (E)

Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, University Sapienza, Rome, Italy.

Ilaria Marzinotto (I)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Vito Lampasona (V)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Ludovica Dottori (L)

Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, University Sapienza, Rome, Italy.

Elena Bazzigaluppi (E)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Cristina Brigatti (C)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Massimiliano Secchi (M)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Lorenzo Piemonti (L)

San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Laura Conti (L)

Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, University Sapienza, Rome, Italy.

Emanuela Pilozzi (E)

Department of Pathology, University Sapienza, Rome, Italy.

Howard W Davidson (HW)

Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Janet M Wenzlau (JM)

Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Bruno Annibale (B)

Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, University Sapienza, Rome, Italy.

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