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.