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


Autoři: Juuso Rusanen aff001;  Anne Toivonen aff002;  Jussi Hepojoki aff001;  Satu Hepojoki aff001;  Pekka Arikoski aff005;  Markku Heikkinen aff006;  Outi Vaarala aff007;  Jorma Ilonen aff008;  Klaus Hedman aff001
Působiště autorů: University of Helsinki, Medicum, Department of Virology, Helsinki, Finland aff001;  Laboratory Services (HUSLAB), Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland aff002;  Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland aff003;  Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland aff004;  Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland aff005;  Department of Gastroenterology, Kuopio University Hospital, Kuopio, Finland aff006;  Clinicum, University of Helsinki, Helsinki, Finland aff007;  Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland aff008
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225851

Souhrn

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.

Klíčová slova:

Autoimmune diseases – Biopsy – Diagnostic medicine – Energy transfer – Enzyme-linked immunoassays – Serodiagnosis – Celiac disease – Enzyme immunoassay


Zdroje

1. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am. J. Gastroenterol. 2013;108: 656–676. doi: 10.1038/ajg.2013.79 23609613

2. Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut. 2014;63: 1210–1228. doi: 10.1136/gutjnl-2013-306578 24917550

3. Downey L, Houten R, Murch S, Longson D. Recognition, assessment, and management of coeliac disease: summary of updated NICE guidance. Br. Med. J. 2015;351: h4513. doi: 10.1136/bmj.h4513 26333593

4. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J. Pediatr. Gastroenterol. Nutr. 2012;54: 136–160. doi: 10.1097/MPG.0b013e31821a23d0 22197856

5. Lebwohl B, Sanders DS, Green PHR. Coeliac disease. 2018;391: 70–81. doi: 10.1016/S0140-6736(17)31796-8

6. Fuchs V, Kurppa K, Huhtala H, Laurila K, Maki M, Collin P, et al. Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities. Aliment. Pharm. Ther. 2019;49: 277–284. doi: 10.1111/apt.15109 30592070

7. Trovato CM, Montuori M, Anania C, Barbato M, Vestri AR, Guida S, et al. Are ESPGHAN "Biopsy-Sparing" Guidelines for Celiac Disease also Suitable for Asymptomatic Patients? Am. J. Gastroenterol. 2015;110: 1485–1489. doi: 10.1038/ajg.2015.285 26372508

8. Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment. Pharm. Ther. 2009;31: 73–81. doi: 10.1111/j.1365-2036.2009.04110.x 19664074

9. Singh P, Arora A, Strand TA, Leffler DA, Maki M, Kelly CP, et al. Diagnostic Accuracy of Point of Care Tests for Diagnosing Celiac Disease: A Systematic Review and Meta-Analysis. J. Clin. Gastroenterol. 2019;53: 535–542. doi: 10.1097/MCG.0000000000001081 29912751

10. Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin. Gastroenterol. Hepatol. 2018;16: 823–836.e2. doi: 10.1016/j.cgh.2017.06.037 29551598

11. Gray AM, Papanicolas IN. Impact of symptoms on quality of life before and after diagnosis of coeliac disease: results from a UK population survey. BMC Health. Serv. Res. 2010;10: 105. doi: 10.1186/1472-6963-10-105 20423498

12. Norstrom F, Lindholm L, Sandstrom O, Nordyke K, Ivarsson A. Delay to celiac disease diagnosis and its implications for health-related quality of life. BMC Gastroenterol. 2011;11: 118. doi: 10.1186/1471-230X-11-118 22060243

13. Vavricka SR, Vadasz N, Stotz M, Lehmann R, Studerus D, Greuter T, et al. Celiac disease diagnosis still significantly delayed—Doctor's but not patients' delay responsive for the increased total delay in women. Digest. Liver Dis. 2016;48: 1148–1154. doi: 10.1016/j.dld.2016.06.016 27401607

14. Paarlahti P, Kurppa K, Ukkola A, Collin P, Huhtala H, Maki M, et al. Predictors of persistent symptoms and reduced quality of life in treated coeliac disease patients: a large cross-sectional study. BMC Gastroenterol. 2015;13: 75. doi: 10.1186/1471-230x-13-75 23631482

15. Fuchs V, Kurppa K, Huhtala H, Maki M, Kekkonen L, Kaukinen K. Delayed celiac disease diagnosis predisposes to reduced quality of life and incremental use of health care services and medicines: A prospective nationwide study. United Eur. Gastroent. 2018;6: 567–575. doi: 10.1177/2050640617751253 29881612

16. Hemmila I, Laitala V. Progress in lanthanides as luminescent probes. J. Fluoresc. 2005;15: 529–542. doi: 10.1007/s10895-005-2826-6 16167211

17. Hepojoki S, Nurmi V, Vaheri A, Hedman K, Vapalahti O, Hepojoki J. A Protein L -Based Immunodiagnostic Approach Utilizing Time-Resolved Forster Resonance Energy Transfer. PLOS One. 2014;9: e106432. doi: 10.1371/journal.pone.0106432 25181527

18. Hepojoki S, Hepojoki J, Hedman K, Vapalahti O, Vaheri A. Rapid Homogeneous Immunoassay Based on Time-Resolved Forster Resonance Energy Transfer for Serodiagnosis of Acute Hantavirus Infection. J. Clin. Microbiol. 2015;53: 636–640. doi: 10.1128/JCM.02994-14 25520445

19. Kareinen L, Hepojoki S, Huhtamo E, Korhonen EM, Schmidt-Chanasit J, Hedman K, et al. Immunoassay for serodiagnosis of Zika virus infection based on time-resolved Forster resonance energy transfer. PLOS One. 2019;14: e0219474. doi: 10.1371/journal.pone.0219474 31335898

20. Kiviniemi M, Nurmi J, Lovgren T, Ilonen J. Locked nucleic acid (LNA) probes in high-throughput genetic analysis: Application to an assay for type 1 diabetes-related HLA-DQB1 alleles. Clin. Biochem. 2005;38: 1015–1022. doi: 10.1016/j.clinbiochem.2005.08.001 16137668

21. Nejentsev S, Sjoroos M, Soukka T, Knip M, Simell O, Lovgren T, et al. Population-based genetic screening for the estimation of Type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci. Diabetic Med. 1999;16: 985–992. doi: 10.1046/j.1464-5491.1999.00186.x 10656226

22. Saraheimo S, Hepojoki J, Nurmi V, Lahtinen A, Hemmilä I, Vaheri A, et al. Time-Resolved FRET -Based Approach for Antibody Detection–A New Serodiagnostic Concept. PLOS One. 2013;8: e62739. doi: 10.1371/journal.pone.0062739 23667515

23. Leffler DA, Schuppan D. Update on Serologic Testing in Celiac Disease. Am. J. Gastroenterol. 2010;105: 2520–2524. doi: 10.1038/ajg.2010.276 21131921


Článek vyšel v časopise

PLOS One


2019 Číslo 11