Electrochemical Immunosensors for the Diagnosis of Celiac Disease

Abstract

Celiac disease is a permanent intolerance to gluten proteins of wheat, rye, barley, and oats in genetically susceptible individuals. The clinical picture is characterized by inflammation and damage of the small intestinal mucosa and malabsorption of essential nutrients. Therapeutically, a lifelong strict gluten-free diet is necessary. The diagnosis of celiac disease is complex and includes symptomatology, serology, small intestinal histology, and genetic status. Serological testing plays a central role within the diagnostic procedure and is based on the measurement of disease-specific antibodies against gluten proteins (antigen) and tissue transglutaminase (autoantigen). Immunofluorescence detection and enzyme-linked immunosorbent assays are currently most often applied for antibody testing. However, these tests are expensive and time-consuming. Therefore, simple and rapid alternative methods have been developed during the last years, and electro-chemical immunosensors seem to be the most promising analytical tools. The architecture of these sensors may comprise the following elements: working and reference electrodes, covalent or noncovalent binding of the antigen to the surface of the working electrode by means of a functional monolayer, and blocking of unreacted binding sites. The analytical procedure is initiated by adding the analyte (serum antibodies) and an analyte-specific second antibody, which is usually labeled with an enzyme. The special reaction of the enzyme with an appropriate substrate results in a product that initiates a current that can be measured by different electrical methods. A number of different electrochemical immunosensors variable in different electrodes, binding systems, secondary antibodies, and current measurements have been developed. Most of them have been tested with real human serum samples of celiac patients and healthy individuals, and some of them reached disease sensitivity and specificity comparable with traditional analytical systems. Thus, electrochemical immunosensors can be promising alternatives to existing diagnostic tests in the future. They are simple, reliable, robust, user-friendly, and cost-effective tools with short operation times.

Share and Cite:

Scherf, K. , Koehler, P. and Wieser, H. (2015) Electrochemical Immunosensors for the Diagnosis of Celiac Disease. Advances in Chemical Engineering and Science, 5, 83-95. doi: 10.4236/aces.2015.51009.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Wieser, H., Koehler, P. and Konitzer, K. (2014) Celiac Disease and Gluten. Multidisciplinary Challenges and Opportunities. Academic Press, Amsterdam, New York, San Diego.
[2] Husby, S., Koletzko, S., Korponay-Szabo, I.R., Mearin, M.L., Phillips, A., Shamir, R., Troncone, R., Giersiepen, K., Branski, D., Catassi, C., Lelgeman, M., Maki, M., Ribes-Koninckx, C., Ventura, A. and Zimmer, K.P. (2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease. Journal of Pediatric Gastroenterology and Nutrition, 54, 136-160.
http://dx.doi.org/10.1097/MPG.0b013e31821a23d0
[3] Giersiepen, K., Lelgemann, M., Stuhldreher, N., Ronfani, L., Husby, S., Koletzko, S. and Korponay-Szabo, I.R. (2012) Accuracy of Diagnostic Antibody Tests for Coeliac Disease in Children: Summary of Evidence Report. Journal of Pediatric Gastroenterology and Nutrition, 54, 229-241.
http://dx.doi.org/10.1097/MPG.0b013e318216f2e5
[4] Rozenberg, O., Lerner, A., Pacht, A., Grinberg, M., Reginashvilli, D., Hening, C. and Barak, M. (2012) A Novel Algorithm for the Diagnosis of Celiac Disease and a Comprehensive Review of Celiac Disease Diagnostics. Clinical Reviews in Allergy & Immunology, 42, 331-341.
http://dx.doi.org/10.1007/s12016-010-8250-y
[5] Luppa, P.B., Sokoll, L.J. and Chan, D.W. (2001) Immunosensors—Principles and Applications to Clinical Chemistry. Clinica Chimica Acta, 314, 1-26.
http://dx.doi.org/10.1016/S0009-8981(01)00629-5
[6] Bange, A., Halsall, H.B. and Heineman, W.R. (2005) Microfluidic Immunosensor Systems. Biosensors and Bioelectronics, 20, 2488-2503.
http://dx.doi.org/10.1016/j.bios.2004.10.016
[7] Balkenhohl, T. and Lisdat, F. (2007) An Impedimetric Immunosensor for the Detection of Autoantibodies Directed against Gliadins. Analyst, 132, 314-322.
http://dx.doi.org/10.1039/b609832k
[8] Rosales-Rivera, L.C., Acero-Sanchez, J.L., Lozano-Sanchez, P., Katakis, I. and O’Sullivan, C.K. (2011) Electrochemical Immunosensor Detection of Antigliadin Antibodies from Real Human Sera. Biosensors and Bioelectronics, 26, 4471-4476.
http://dx.doi.org/10.1016/j.bios.2011.05.004
[9] Neves, M.M.P.S., Gonzales-Garcia, M.B., Santos-Silva, A. and Costa-Garcia, A. (2012) Voltammetric Immunosensors for the Diagnosis of Celiac Disease Based on the Quantification of Anti-Gliadin Antibodies. Sensors and Actuators B, 163, 253-259.
http://dx.doi.org/10.1016/j.snb.2012.01.048
[10] Schwertz, E., Kahlenberg, F., Sack, U., Richter, T., Stern, M., Conrad, K., Zimmer, K.-P. and Mothes, T. (2004) Serologic Assay Based on Gliadin-Related Nonapeptides as a Highly Sensitive and Specific Diagnostic Aid in Celiac Disease. Clinical Chemistry, 50, 2370-2375.
http://dx.doi.org/10.1373/clinchem.2004.036111
[11] Neves, M.M.P.S., Gonzales-Garcia, M.B., Nouws, H.P.A. and Costa-Garcia, A. (2013) An Electrochemical Deamidated Gliadin Antibody Immunosensor for Celiac Disease Clinical Diagnosis. Analyst, 138, 1956-1958.
http://dx.doi.org/10.1039/c3an36728b
[12] Dorum, S., Qiao, S.W., Sollid, L.M. and Fleckenstein, B. (2009) A Quantitative Analysis of Transglutaminase 2-Mediated Deamidation of Gluten Peptides: Implications for the T-Cell Response in Celiac Disease. Journal of Proteome Research, 8, 1748-1755.
http://dx.doi.org/10.1021/pr800960n
[13] Constantini, F., Nascetti, A., Scipinotti, R., Domenici, F., Sennato, S., Gazza, L., Bordi, F., Pogna, N., Manetti, C., Caputo, D. and De Cesare, G. (2014) On-Chip Detection of Multiple Serum Antibodies against Epitopes of Celiac Disease by an Array of Amorphous Silicon Sensors. RCS Advances, 4, 2073-2080.
[14] Dieterich, W., Ehnis, T., Bauer, M., Donner, P., Volta, U., Riecken, E.O. and Schuppan, D. (1997) Identification of Tissue Transglutaminase as the Autoantigen of Celiac Disease. Nature Medicine, 3, 797-801.
http://dx.doi.org/10.1038/nm0797-797
[15] Balkenhohl, T. and Lisdat, F. (2007) Screen-Printed Electrodes as Impedimetric Immunosensors for the Detection of Anti-Transglutaminase Antibodies in Human Sera. Analytica Chimica Acta, 597, 50-57.
http://dx.doi.org/10.1016/j.aca.2007.06.041
[16] Pividori, M.I., Lermo, A., Bonnani, A., Alegret, S. and Del Valle, M. (2009) Electrochemical Immunosensor for the Diagnosis of Celiac Disease. Analytical Biochemistry, 388, 229-234.
http://dx.doi.org/10.1016/j.ab.2009.02.026
[17] Dulay, S., Lozano-Sanchez, P., Iwuoha, E., Katakis, I. and O’Sullivan, C.K.O. (2011) Electrochemical Detection of Celiac Disease-Related Anti-Tissue Transglutaminase Antibodies Using Thiol Based Surface Chemistry. Biosensors and Bioelectronics, 26, 3852-3856.
http://dx.doi.org/10.1016/j.bios.2011.02.045
[18] West, N., Baker, P.G.L., Arotiba, O.A., Hendricks, N.R., Baleg, A.A., Waryo, T.T., Ngece, R.F., Iwuoha, E.I. and O’Sullivan, C. (2011) Overoxidized Polypyrrole Incorporated with Gold Nanoparticles as Platform for Impedimetric Anti-Transglutaminase Immunosensor. Analytical Letters, 44, 1956-1966.
http://dx.doi.org/10.1080/00032719.2010.539739
[19] Neves, M.M.P.S., Gonzales-Garcia, M.B., Nouws, H.P.A. and Costa-Garcia, A. (2012) Celiac Disease Detection Using a Transglutaminase Electrochemical Immunosensor Fabricated on Nanohybrid Screen-Printed Carbon Electrodes. Biosensors and Bioelectronics, 31, 95-100.
http://dx.doi.org/10.1016/j.bios.2011.09.044
[20] Adornetto, G., Volpe, G., De Stefano, A., Martini, S., Gallucci, G., Manzoni, A., Bernardini, S., Mascini, M. and Moscone, D. (2012) An ELIME Assay for the Rapid Diagnosis of Coeliac Disease. Analytical and Bioanalytical Chemistry, 403, 1191-1194.
http://dx.doi.org/10.1007/s00216-011-5702-z
[21] Kergaravat, S.V., Beltramino, L., Garnero, N., Trotta, L., Wagener, M., Pividori, M.I. and Hernandez, S.R. (2013) Electrochemical Magneto Immunosensor for the Detection of Anti-TG2 Antibody in Celiac Disease. Biosensors and Bioelectronics, 48, 203-209.
http://dx.doi.org/10.1016/j.bios.2013.04.012
[22] Martin-Yerga, D., Gonzales-Garcia, M.B. and Costa-Garcia, A. (2014) Electrochemical Immunosensor for Anti-Tissue Transglutaminase Antibodies Based on the in Situ Detection of Quantum Dots. Talanta, 130, 598-602.
http://dx.doi.org/10.1016/j.talanta.2014.07.010
[23] Pallav, K., Leffler, D.A., Bennett, M., Tariq, S., Xu, H., Kabbani, T., Moss, A.C., Dennis, M., Kelly, C.P. and Schuppan, D. (2012) Open Conformation Tissue Transglutaminase Testing for Celiac Dietary Assessment. Digestive and Liver Disease, 44, 375-378.
http://dx.doi.org/10.1016/j.dld.2011.12.008
[24] Giannetto, M., Mattarozzi, M., Umilta, E., Manfredi, A., Quaglia, S. and Careri, M. (2014) An Amperometric Immunosensor for Diagnosis of Celiac Disease Based on Covalent Immobilization of Open Conformation Tissue Transglutaminase for Determination of Anti-tTG Antibodies in Human Serum. Biosensors and Bioelectronics, 62, 325-330.
http://dx.doi.org/10.1016/j.bios.2014.07.006
[25] Bizzaro, N., Tozzoli, R., Villalta, D., Fabris, M. and Tonutti, E. (2012) Cutting-Edge Issues in Coeliac Disease and in Gluten Intolerance. Clinical Reviews in Allergy & Immunology, 42, 279-287.
http://dx.doi.org/10.1007/s12016-010-8223-1
[26] Neves, M.M.P.S., Gonzales-Garcia, M.B., Delerue-Matos, C. and Costa-Garcia, A. (2013) Multiplexed Electrochemical Immunosensor for Detection of Celiac Disease Serological Markers. Sensors and Actuators B, 187, 33-39.
http://dx.doi.org/10.1016/j.snb.2012.09.019

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.