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Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies

Although it is estimated that more than one million Americans have celiac disease (CD), it remains challenging to diagnose. CD, an autoimmune and inflammatory response following the ingestion of gluten-containing foods, has symptoms overlapping with other diseases and requires invasive diagnostics....

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Autores principales: Nguyen, Anna B. N., Maldonado, Marcos, Poch, Dylan, Sodia, Tyler, Smith, Andrew, Rowland, Teisha J., Bonham, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070315/
https://www.ncbi.nlm.nih.gov/pubmed/33920183
http://dx.doi.org/10.3390/s21082671
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author Nguyen, Anna B. N.
Maldonado, Marcos
Poch, Dylan
Sodia, Tyler
Smith, Andrew
Rowland, Teisha J.
Bonham, Andrew J.
author_facet Nguyen, Anna B. N.
Maldonado, Marcos
Poch, Dylan
Sodia, Tyler
Smith, Andrew
Rowland, Teisha J.
Bonham, Andrew J.
author_sort Nguyen, Anna B. N.
collection PubMed
description Although it is estimated that more than one million Americans have celiac disease (CD), it remains challenging to diagnose. CD, an autoimmune and inflammatory response following the ingestion of gluten-containing foods, has symptoms overlapping with other diseases and requires invasive diagnostics. The gold standard for CD diagnosis involves serologic blood tests followed by invasive confirmatory biopsies. Here, we propose a less invasive method using an electrochemical DNA (E-DNA) biosensor for CD-specific autoantibodies (AABs) circulating in blood. In our approach, CD-specific AABs bind a synthetic neoepitope, causing a conformational change in the biosensor, as well as a change in the environment of an attached redox reporter, producing a measurable current reduction. We assessed the biosensor’s ability to detect CD-specific patient-derived AABs in physiological buffer as well as buffer supplemented with bovine serum. Our biosensor was able to detect AABs in a dose-dependent manner; increased signal change correlated with increased AAB concentration with an apparent dissociation constant of 0.09 ± 0.03 units/mL of AABs. Furthermore, we found our biosensor to be target-specific, with minimal off-target binding of multiple unrelated biomarkers. Future efforts aimed at increasing sensitivity in complex media may build upon the biosensor design presented here to further improve CD AAB detection and CD diagnostic tools.
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spelling pubmed-80703152021-04-26 Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies Nguyen, Anna B. N. Maldonado, Marcos Poch, Dylan Sodia, Tyler Smith, Andrew Rowland, Teisha J. Bonham, Andrew J. Sensors (Basel) Communication Although it is estimated that more than one million Americans have celiac disease (CD), it remains challenging to diagnose. CD, an autoimmune and inflammatory response following the ingestion of gluten-containing foods, has symptoms overlapping with other diseases and requires invasive diagnostics. The gold standard for CD diagnosis involves serologic blood tests followed by invasive confirmatory biopsies. Here, we propose a less invasive method using an electrochemical DNA (E-DNA) biosensor for CD-specific autoantibodies (AABs) circulating in blood. In our approach, CD-specific AABs bind a synthetic neoepitope, causing a conformational change in the biosensor, as well as a change in the environment of an attached redox reporter, producing a measurable current reduction. We assessed the biosensor’s ability to detect CD-specific patient-derived AABs in physiological buffer as well as buffer supplemented with bovine serum. Our biosensor was able to detect AABs in a dose-dependent manner; increased signal change correlated with increased AAB concentration with an apparent dissociation constant of 0.09 ± 0.03 units/mL of AABs. Furthermore, we found our biosensor to be target-specific, with minimal off-target binding of multiple unrelated biomarkers. Future efforts aimed at increasing sensitivity in complex media may build upon the biosensor design presented here to further improve CD AAB detection and CD diagnostic tools. MDPI 2021-04-10 /pmc/articles/PMC8070315/ /pubmed/33920183 http://dx.doi.org/10.3390/s21082671 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Nguyen, Anna B. N.
Maldonado, Marcos
Poch, Dylan
Sodia, Tyler
Smith, Andrew
Rowland, Teisha J.
Bonham, Andrew J.
Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title_full Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title_fullStr Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title_full_unstemmed Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title_short Electrochemical DNA Biosensor That Detects Early Celiac Disease Autoantibodies
title_sort electrochemical dna biosensor that detects early celiac disease autoantibodies
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070315/
https://www.ncbi.nlm.nih.gov/pubmed/33920183
http://dx.doi.org/10.3390/s21082671
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