LFRET, a novel rapid assay for anti-tissue transglutaminase antibody detection

PLoS One. 2019 Nov 26;14(11):e0225851. doi: 10.1371/journal.pone.0225851. eCollection 2019.

Abstract

The diagnosis of celiac disease (CD) is currently based on serology and intestinal biopsy, with detection of anti-tissue transglutaminase (tTG) IgA antibodies recommended as the first-line test. Emphasizing the increasing importance of serological testing, new guidelines and evidence suggest basing the diagnosis solely on serology without confirmatory biopsy. Enzyme immunoassays (EIAs) are the established approach for anti-tTG antibody detection, with the existing point-of-care (POC) tests lacking sensitivity and/or specificity. Improved POC methods could help reduce the underdiagnosis and diagnostic delay of CD. We have previously developed rapid homogenous immunoassays based on time-resolved Förster resonance energy transfer (TR-FRET), and demonstrated their suitability in serodiagnostics with hanta- and Zika virus infections as models. In this study, we set out to establish a protein L -based TR-FRET assay (LFRET) for the detection of anti-tTG antibodies. We studied 74 patients with biopsy-confirmed CD and 70 healthy controls, with 1) the new tTG-LFRET assay, and for reference 2) a well-established EIA and 3) an existing commercial POC test. IgG depletion was employed to differentiate between anti-tTG IgA and IgG positivity. The sensitivity and specificity of the first-generation tTG-LFRET POC assay in detection of CD were 87.8% and 94.3%, respectively, in line with those of the reference POC test. The sensitivity and specificity of EIA were 95.9% and 91.9%, respectively. This study demonstrates the applicability of LFRET to serological diagnosis of autoimmune diseases in general and of CD in particular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Case-Control Studies
  • Celiac Disease / diagnosis*
  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescence Resonance Energy Transfer
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / immunology*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Immunoassay / methods*
  • Point-of-Care Systems
  • Protein Glutamine gamma Glutamyltransferase 2
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Sensitivity and Specificity
  • Transglutaminases / genetics
  • Transglutaminases / immunology*
  • Transglutaminases / metabolism

Substances

  • Autoantibodies
  • Recombinant Proteins
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins

Grants and funding

This work was funded by Special Research Funds for University Hospitals in Finland (to J.I., stm.fi), Päivikki and Sakari Sohlberg Foundation (to J.I., pss-saatio.fi), Sigrid Jusélius Foundation (to J.I. and K.H., sigridjuselius.fi), Medical Society of Finland (FLS) (to K.H., fls.fi), Magnus Ehrnrooth Foundation (to K.H., magnusehrnroothinsaatio.fi), Finnish Society of Sciences and Letters (to K.H., scientiarum.fi), and the Research Funds of University of Helsinki and Helsinki University Hospital (to K.H., hus.fi) and the Academy of Finland (to J.H., grant 1308613, aka.fi). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.