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Karachaliou, C.; Livaniou, E. Immunosensors for Autoimmune-Disease-Related Biomarkers. Encyclopedia. Available online: https://encyclopedia.pub/entry/47606 (accessed on 18 May 2024).
Karachaliou C, Livaniou E. Immunosensors for Autoimmune-Disease-Related Biomarkers. Encyclopedia. Available at: https://encyclopedia.pub/entry/47606. Accessed May 18, 2024.
Karachaliou, Chrysoula-Evangelia, Evangelia Livaniou. "Immunosensors for Autoimmune-Disease-Related Biomarkers" Encyclopedia, https://encyclopedia.pub/entry/47606 (accessed May 18, 2024).
Karachaliou, C., & Livaniou, E. (2023, August 03). Immunosensors for Autoimmune-Disease-Related Biomarkers. In Encyclopedia. https://encyclopedia.pub/entry/47606
Karachaliou, Chrysoula-Evangelia and Evangelia Livaniou. "Immunosensors for Autoimmune-Disease-Related Biomarkers." Encyclopedia. Web. 03 August, 2023.
Immunosensors for Autoimmune-Disease-Related Biomarkers
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This entry is adapted from the peer-reviewed paper 10.3390/s23156770

Autoimmune diseases (ADs) are a group of various disorders that are characterized by dysregulation of the immune system. This malfunction state leads to an improper activation of immune elements that may consequently attack target molecules, cells, and tissues of the organism, resulting in inflammation and organ damage. Due to the continuously increasing number of patients with ADs, the severity of ADs’ clinical symptoms, and treatment insufficiency, novel analytical tools enabling early, reliable, and high-throughput disease diagnosis are highly desirable, since such tools may help health systems to confront the burden related to the late diagnosis of ADs and decrease premature mortality. To meet this need, during the last two decades, several immunosensors for detecting AD-related biomarkers have been developed as research prototypes. The AD immunosensors reported to date can be divided into two main categories depending on the biomarker(s) detected, i.e., either various autoantibodies or other protein biomarkers, such as specific inflammation-related cytokines. Most of AD immunosensors are electrochemical, while some optical and a few piezoelectric sensors have also been described.

autoantibodies autoimmune diseases patients’ biological fluids immunosensors inflammation protein-biomarkers

1. Introduction

Autoimmune diseases (ADs) are a group of various disorders that are characterized by dysregulation of the immune system. This malfunction state leads to an improper activation of immune elements that may consequently attack target molecules, cells, and tissues of the organism, resulting in inflammation and organ damage [1]. ADs are considered chronic disorders that develop over several years [2] and may be divided into organ-specific or multi-organ/systemic [3]. Thus, in type 1 diabetes (T1D) [4], an organ-specific AD, the autoimmunity-related inflammatory responses of the organism are specifically directed against the β-islet cells of the pancreas, which are eventually destroyed, leading to insulin deficiency. By comparison, in rheumatoid arthritis (RA) [5], a multi-organ/systemic autoimmune disease, inflammation is “dispersed” to the joints of the organism, as the synovial membrane is infiltrated by activated immune cells. According to the literature [6], some ADs exhibit both systemic and organ-specific characteristics; for instance, multiple sclerosis (MS) [7] is characterized by inflammation in the brain and spinal cord, which results in neuron axon and myelin damage in the central nervous system, and, consequently, general disturbances [6]. Usually, ADs follow a pattern of progressively increased severity, while the insufficiency of the treatment protocols available at present, combined with autoimmune attack of vital organs, such as lungs and kidneys, may eventually lead to a fatal outcome [1].
ADs are currently estimated to affect almost 5–7% of the world population, while it is well accepted that their prevalence will continue to rise worldwide in the following years [6]. The etiology of ADs is basically unknown, but it has mainly been associated with genetic and epigenetic factors along with environmental ones, such as nutritional habits and air pollution [6]. Moreover, it is widely accepted that specific viral infections can cause development of ADs [6]. For instance, infection with Epstein–Barr virus has been associated with the pathogenesis of RA [8] and MS [9]. Furthermore, several literature reports associate the SARS-CoV-2 virus, which caused the recent pandemic, with development of autoimmunity/autoantibodies [10][11][12]. Nevertheless, the exact mechanisms by which certain viruses may trigger the onset of ADs have not yet been well elucidated.

Biomarkers and Analytical Tools

ADs are closely associated with the generation of autoantibodies against certain self-antigens that can subsequently attack cells, tissues, and organs of the organism. Many autoantibodies have been associated with pathogenesis/treatment of specific ADs, such as systemic lupus erythematosus (SLE) [13]. Moreover, a series of autoantibodies has been proposed to serve as diagnostic biomarkers for ADs [14][15][16]; specifically, various anti-citrullinated protein/peptide antibodies (ACPAs) and rheumatoid factors (RFs), i.e., IgM, IgA, and IgG antibodies directed against the Fc fragment of the patient’s own IgG molecules, were included in the classification criteria for RA set by the European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) [17][18][19].
Production of inflammatory protein mediators is considered a common feature of ADs. Thus, pathogenesis of RA has been closely related to various inflammatory proteins, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while several interleukins, including interleukin-1 (IL-1), IL-6, interleukin-8 (IL-8), interleukin12 (IL-12), and interleukin-32 (IL-32), have been proposed as promising biomarkers of a series of rheumatic ADs [20][21][22][23][24]. Other protein-biomarkers have been associated with diagnosis/prognosis/follow-up of specific ADs; for instance, the protein hormone insulin has been correlated with the diagnosis of various types of diabetes and its low circulating levels have been proposed to signify T1D [25].
All the above-mentioned AD biomarkers are of a protein nature; however, microRNAs, extracellular vesicles/exosomes, etc., have also been proposed for the diagnosis of specific ADs, such as RA, MS, and T1D [26][27][28].
Due to the wide prevalence and severity of symptoms of ADs, demand for analytical tools detecting AD-related biomarkers and enabling early and reliable diagnosis of the disease state is very high and expected to further increase in the close future. To date, the methods most frequently used for determining AD biomarkers of a protein nature are immunoassays and, in particular, ELISAs, while other biochemical assays, such as Western blot, have been also reported. The disadvantages of these methods often include low sensitivity, along with time-consuming, laborious, and complex protocols; moreover, most of these methods require skilled personnel and well-equipped laboratories. Therefore, during the last two decades, attention has focused on developing biosensors that are specific, sensitive, reproducible, and stable, as well as simple, fast, and low-cost, for the determination of protein-type AD biomarkers in complex clinical samples, such as blood sera, preferably at the point of care [1][29].
Biosensors are analytical devices that employ specific biomolecules for recognizing the target entity; biosensors integrate the biorecognition element with suitable transducers, which could be further enriched with various signal amplification systems to achieve extremely high sensitivity. Immunosensors are a special class of biosensors that employ specific antibodies as the biorecognition part; upon specific recognition and capture of the target analyte, a series of physical and/or chemical changes is induced, which could be converted into detectable signals by an appropriate transducer.
Depending on the type of transducer employed, biosensors/immunosensors can be characterized as electrochemical, optical, piezoelectric, or thermal [1][24][29][30][31][32]. In electrochemical biosensors/immunosensors, recognition and binding of the target analyte to its specific partner biomolecule usually causes a change in the electron transfer rate between a properly functionalized electrode surface and an electrolyte solution; this change can be detected as a current (amperometric sensors), charge accumulation or potential (potentiometric sensors), or change in conductivity (conductimetric/impedimetric sensors). Electrochemical biosensors/immunosensors have many advantages, including high analytical sensitivity and specificity, rapid assay protocol, low quantity of sample needed, and potential of developing miniaturized devices for point-of-care analyses. In optical biosensors/immunosensors, recognition/binding of the target analyte to the partner biomolecule causes measurable changes in the phase, amplitude, polarization, or frequency of the input light. Optical immunosensors include colorimetric, fluorescent, luminescent, and reflectometric/refractometric sensors [31]. Optical biosensors/immunosensors also have a series of desired characteristics, such as high sensitivity, high specificity, and rapid assay protocol, but their instrumentation is often bulky and expensive; nevertheless, much work has been recently devoted to address these limitations and enhance optical sensors’ applicability. In piezoelectric biosensors/immunosensors, recognition/binding of the target analyte usually causes a mass change on the sensing surface of the device. These sensors, which are usually based on quartz crystal microbalance (QCM) resonators, are not as widely used as the electrochemical and optical ones, mainly because of the complexity of their assay protocol. Thermal biosensors are based on the heat energy absorbed or released in biochemical reactions [32] and have very rarely been used in the field of diagnosis. It should be noted that various nanomaterials with desired features have been employed in the design/construction of biosensors/immunosensors, especially electrochemical and optical ones, aiming at further improving the analytical sensitivity and specificity of the latter [33][34][35].
Several review articles have presented biosensors/immunosensors for ADs, some of which deal only with electrochemical sensors, while others present information on sensors based on more types of signal transduction [1][3][24][36]. Some recent reviews have described biosensors/immunosensors proposed to serve diagnosis of specific ADs, such as MS [37][38] and RA [39], while other review papers have focused on biosensors/immunosensors for the detection of specific AD-related biomarkers, such as IL-6 [23].

2. AD Immunosensors Detecting Autoantibodies

AD immunosensors detecting autoantibodies are mainly electrochemical, although some optical and piezoelectric-type sensors have been reported. Concerning the immunoassay principle, all sensors are non-competitive and based on the direct binding between an appropriate derivative of the “self-antigen” and the relevant autoantibody, which is actually the assay analyte. Keeping this in mind, one should note that, in a way, all affinity-based biosensors that detect autoantibodies can, by definition, be considered as immunosensors, i.e., even if they do not employ “external” antibodies as assay reagents. In many sensors, however, a secondary antibody is indeed employed, either labeled or not, which is added to the predominant immunocomplex, mostly to enhance the assay signal. In such immunosensors, the actual immunoassay setting is antigen–autoantibody/analyte–secondary antibody.
Regarding the most recently reported AD immunosensors that can detect autoantibodies (from 2019 to now), some points to note are discussed below in brief:
An electrochemical immunosensor for autoantibodies against oncostatin-M receptor (OSMR), which has been associated with the AD known as systemic sclerosis [40], was developed. The sensor was based on tin dopped indium (ITO) electrodes coated with a conductive layer of poly-pyrrole (PPy); PPy was suitably loaded with gold nanoparticles, on which OSMR was immobilized, so as to capture the corresponding autoantibodies [41]. ACPAs, a well-known biomarker of RA, as already mentioned, were detected by an electrochemical immunosensor using interdigitated electrodes, the surfaces of which were suitably modified with a cyclic citrullinated peptide loaded on iron oxide nanoparticles. The nanoparticles were synthesized with a “green-chemistry” approach based on a plant extract and chemically immobilized on the sensing surface by means of 3-aminopropyltriethoxysilane and glutaraldehyde [18]. Another electrochemical immunosensor for the detection of ACPAs was based on electrodes, the surfaces of which were functionalized with avidin. Avidin was covalently immobilized on the sensing surface, which had been covered with a self-assembled monolayer of mercaptohexanoic acid through N-hydroxy succinimide/1-ethyl-3-(3-diethylamino)propyl carbodiimide. A biotinylated cyclic citrullinated peptide was bound on the functionalized surface, which could subsequently capture/detect any anti-citrullinated peptide/protein autoantibodies present in the biological sample [42]. A customized quartz crystal microbalance (QCM) point-of-care immunosensor was developed for autoantibodies against the phospholipase A2 receptor (anti-PLA2R), which has been reported to serve as a biomarker in primary membranous nephropathy [43]. The sensor was based on QCM chips coated with reduced graphene oxide; the sensing surface was functionalized through bovine serum albumin adsorption, activation with N-hydroxysuccinimide/1-ethyl-3-(3-diethylamino)propyl carbodiimide, and covalent immobilization of the dominant epitope of PLA2R on the activated surface, which could subsequently capture the anti-PLA2R autoantibodies present in samples to be analyzed [44]. A multiplex, label-free optical immunosensor was developed on microarray glass biochips and applied to both detection and activity characterization of several autoantibodies in the same biological sample. Simultaneous detection of two antibodies that have been associated with thyroid ADs, and especially Hashimoto’s thyroiditis [45], i.e., anti-thyroglobulin (anti-TG) and anti–thyroid peroxidase (anti-TPO) model autoantibodies, was reported. As already mentioned, the sensor could be applied to both quantitating the autoantibodies and evaluating binding kinetics with the corresponding free self-antigen, thus providing more comprehensive diagnostic information [46]. An immunosensor based on impedimetric-interdigitated wave type microelectrode array (IDWμE) was developed and applied to the detection of the rheumatoid factor-immunoglobulin M (IgM-RF) autoantibodies. The IDWμE sensing surface was first functionalized through a self-assembled monolayer of thioctic acid, on which IgG-Fc fragments were covalently immobilized and served as specific “self-antigens”/binders to capture the IgM-RF analyte. In the presence of a suitable redox probe, impedimetric measurements showed a significant change upon IgM-RF binding [47]. An optical immunosensor for IgM-RF was based on gold nanoparticles, on which IgG-Fc was covalently linked through a bi-functional polyethylene glycol derivative. In the presence of pentameric IgM-RF, extensive aggregation of functionalized gold nanoparticles occurred, which resulted in a color change [48]. An immunosensor for the detection of IgG-type autoantibodies against tissue transglutaminase (anti-tTG), which is a reliable serological marker of the gluten-associated AD known as celiac disease [49], was described. The sensor was based on membrane-templated gold nanoelectrodes of composite nature. On the polycarbonate part of the sensor surface used to prepare the nanoelectrode ensembles, the tTG-antigen was immobilized and subsequently used to capture the corresponding autoantibodies. The immune complex was finally electrochemically detected through an HRP-labeled secondary antibody, in the presence of the H2O2/hydroxyquinone system [50]. “Sick” red blood cells that bear specific autoantibodies and are present in blood of patients with autoimmune hemolytic anemia [51] have been detected by means of an electrochemical immunosensor [52], which might provide more information in comparison with that revealed by other serological diagnostic tests for this AD [53]. Finally, an electrochemiluminescent (ECL) immunosensor was reported for the detection of autoantibodies against myeloperoxidase (anti-MPO), which are present in patients with an AD known as antineutrophil cytoplasm antibody (ANCA)-associated vasculitides [54]. In this sensor, human MPO was immobilized onto glassy carbon electrodes suitably functionalized with gold/MoS2 nanosheets, and used to capture mouse anti-human MPO (model autoantibody/analyte). Afterward, a secondary antibody loaded on PtCo nanocubes/reduced graphene oxide hybrids, along with a thiol-modified single-stranded DNA, which triggered a hybridization chain reaction (HCR) to form double-stranded DNA that intercalated doxorubicin/N-(aminobutyl)-N-(ethylisoluminol) (ABEI) luminophores, was used to detect the immunocomplexes formed, through ECL signal generation and amplification in the presence of H2O2 [55].
Table 1 presents most of AD immunosensors reported to date that can detect autoantibodies in various samples.
Table 1. AD immunosensors that can detect specific autoantibodies.
Type of Signal Transduction Immunoassay Principle—Use of Secondary Antibody Autoantibody-Biomarker Limit of Detection (LoD)/
Concentration Range		 Autoimmune Disease Biological Sample References
Electrochemical
(Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS))		 Non-competitive, direct-type assay Anti-oncostatin-M receptor autoantibodies - Systemic sclerosis (SSc) Human serum from healthy individuals and SSc patients [41]
Electrochemical (Voltammetry) Non-competitive, direct-type assay Anti-citrullinated peptide/protein autoantibodies
(ACPAs)		 15 pg mL−1/
8–250 pg mL−1		 Rheumatoid arthritis (RA) Human serum (spiked) [18]
Electrochemical (EIS) Non-competitive, direct-type assay ACPAs 0.82 IU ** mL−1/
1–800 IU mL		 RA Human
serum (spiked)		 [42]
Optical
(Spectral correlation interferometry—SCI)		 Non-competitive, direct-type assay; a non-labeled secondary antibody was used Anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) autoantibodies 6 IU mL−1 (anti-TG)
1.7 IU mL−1 (anti-TPO)/
6–400 IU mL−1 (anti-TG)
1.7–860 IU mL−1 (anti-TPO)		 Autoimmune thyroid diseases Patients’ serum [46]
Piezoelectric quartz-crystal microbalance Non-competitive, direct-type assay Anti-phospholipase A2 receptor (anti-PL2R) autoantibodies 0.1 μg mL−1/
0.5–100 μg mL−1		 Primary membranous nephropathy (pMN) Patients’ serum [44]
Electrochemical (EIS) Non-competitive, direct-type assay Immunoglobulin M—rheumatoid factor (IgM-RF) 0.22 IU mL−1/
10–200 IU mL−1		 RA Human
serum (spiked)		 [47]
Electrochemical (Voltammetry) Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tissue transglutaminase (anti-tTG) autoantibodies 1.8 ng mL−1/
0.005–1 μg mL−1		 Celiac disease (CD) Serum from healthy individuals and CD patients [50]
Electrochemical (Impedance spectroscopy and square wave voltammetry) Non-competitive, direct-type assay Autoantibodies on red blood cells (RBCs) - Autoimmune hemolytic anemia Healthy and “sick” RBCs (i.e., RBCs from healthy and affected individuals) [52]
Optical (Colorimetry) Non-competitive, direct-type assay IgM-RF 4.15 IU mL−1 RA Human plasma (spiked) [48]
Electrochemical (Electro-chemiluminescence—ECL) Non-competitive, direct-type assay *; a labeled secondary antibody was used Anti-myeloperoxidase (anti-MPO)
autoantibodies		 15.68 fg mL−1/
50 fg mL−1–1 ng mL−1		 Anti-neutrophil cytoplasm antibody-associated vasculitides Human serum (spiked) [55]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay *; a labeled secondary antibody was used Anti-double-stranded DNA (anti-dsDNA)
autoantibodies		 8 μg mL−1 Systemic lupus erythematosus (SLE) Patients’ serum [56]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tTG autoantibodies
(IgG and IgA)		 1.4 AU ** mL−1 (IgG) and 3.2 AU mL−1 (IgA)/
up to 30 AU mL−1 (IgG and IgA)		 CD Patients’ serum

 [57]
Electrochemical (Electro-chemiluminescence—ECL) Non-competitive, direct-type assay Anti-glutamate decarboxylase (anti-GAD) autoantibodies 0.10 ng mL−1/
0.30–50 ng mL−1		 Type-1 diabetes (T1D) or latent autoimmune diabetes in adult Patients’ serum [58]
Piezoelectric Quartz-crystal microbalance Non-competitive, direct-type assay Anti-TRIM21 and anti-TROVE2 autoantibodies 0.01 U ** mL−1 (anti-TRIM21) 0.005 U mL−1 (anti-TROVE2)/
0.32–7.17 U mL−1 (anti-TRIM21)
0.07–1.46 U mL−1 (anti-TROVE2)		 SLE Serum from healthy individuals and SLE patients [59]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tTG autoantibodies 0.26 μg mL−1/
0.26–6.9 μg mL−1		 CD Serum from CD patients [60]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tTG autoantibodies (IgA and IgG) 1.7 AU mL−1 (IgA) and 2.7 AU mL−1 (IgG)/
Up to 30 AU mL−1 (IgA and IgG)		 CD Serum from pediatric patients [61]
Electrochemical (EIS) Non-competitive, direct-type assay Anti-Myelin Basic Protein (anti-MBP) autoantibodies 0.1495 ng mL−1/
0.4875–2500 ng mL−1		 Multiple sclerosis (MS) Cerebrospinal fluid (CSF) and serum from relapsing/remitting MS patients [62]
Electrochemical
(CV)		 Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tTG autoantibodies - CD Serum from CD patients [63]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay *; a labeled secondary antibody was used Anti-tTG autoantibodies 390 ng mL−1 CD Serum from CD patients [64]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay *; a labeled secondary antibody was used ACPAs - RA Serum from RA patients [65]
Piezoelectric Quartz-crystal microbalance Non-competitive, direct-type assay ACPAs - RA Serum from RA patients [66]
Electrochemical (EIS) Non-competitive, direct-type assay; a labeled secondary antibody was used Anti-tTG autoantibodies - CD Serum from CD patients [67]
Piezoelectric Quartz-crystal microbalance Non-competitive, direct-type assay Anti-dsDNA
autoantibodies		 - SLE Serum from healthy individuals and patients with bronchial asthma and SLE [68]
Optical
(Surface plasmon resonance–SPR)		 Non-competitive, direct-type assay Anti-GAD autoantibodies - T1D (Buffer) [69]
* In the original papers, the immunocomplexes formed (antigen–autoantibody/analyte–secondary antibody) were characterized as “sandwich”. ** U: units; IU: international units; AU: arbitrary/antibody units.
Several immunosensors detecting antibodies against the wheat grain protein, gliadin [70][71][72], have often been characterized as AD immunosensors, because the anti-gliadin antibodies can serve as CD biomarkers, as anti-tTG autoantibodies do. Strictly speaking, however, anti-gliadin antibodies may not be considered autoantibodies, since gliadin is a food component, not a mammalian self-antigen.
In addition to the aforementioned AD immunosensors, sensors based on similar technological approaches that can detect cancer-related autoantibodies, such as anti-p53 antibodies, have been developed [73]. Comprehensive reviews focusing on biosensors/immunosensors for AD- and cancer-related autoantibodies have been recently published [1][15].

3. AD Immunosensors Detecting Other Protein Biomarkers

Almost all AD immunosensors detecting specific protein biomarkers, other than autoantibodies, are electrochemical, while they are all based on a non-competitive assay principle, of either direct- or sandwich-type. Regarding the most recently reported AD immunosensors (from 2019 to now) of this category, the following can be summarized:
An optical immunosensor was developed for the simultaneous determination of procalcitonin (PCT) and IL-6, which are well-known biomarkers of inflammatory diseases, including ADs. Silicon chips with silicon dioxide areas of different thickness were used, each functionalized with either anti-PCT or anti-IL-6 capture antibodies. Moreover, biotinylated detection antibodies were used along with streptavidin and biotinylated bovine serum albumin, to achieve amplification of the optical signal, in a sandwich-type immunoassay setting [74]. Earlier, an electrochemical immunosensor for IL-6 was developed. The sensor was based on a working electrode modified with a hybrid of gold nanoparticles (AuNPs) and graphene. Magnetic beads loaded with capture anti-IL-6 antibodies were also used, on which IL-6 could be bound and subsequently detected through biotinylated anti-IL-6 antibodies (sandwich-type assay setting) and HRP-labeled streptavidin [22]. An electrochemical immunosensor for oncostatin-M receptor, a soluble form of which (sOSMR) had been found at increased levels in sera of patients with systemic sclerosis, was based on a conductive poly-pyrrole layer loaded with gold nanoparticles, on which anti-sOSMR antibodies were immobilized through cysteine chemisorption [41]; this sensor has been already mentioned (i.e., in “2. AD Immunosensors Detecting Autoantibodies”), since, after a slight modification of the assay format/protocol, it may also be applied to the detection of autoantibodies against sOSMR [41]. Another electrochemical immunosensor was developed for simultaneous determination of the cytokines B-cell activation factor (BAFF) and a proliferation-induced ligand (APRIL), both of which have been associated with systemic lupus erythematosus (SLE) [75]. Biotinylated anti-BAFF and anti-APRIL capture antibodies were loaded onto magnetic beads through neutravidin or direct covalent immobilization, respectively, while detection anti-BAFF antibodies along with HRP-labeled secondary antibodies, and detection biotinylated anti-APRIL antibodies along with HRP-labeled streptavidin, were used for assaying BAFF and APRIL, respectively [76]. In another electrochemical immunosensor for simultaneous determination of BAFF and APRIL, biotinylated anti-BAFF and biotinylated anti-APRIL capture antibodies were indirectly immobilized onto the working electrodes, on which neutravidin had been covalently bound. A sandwich-type assay setting was achieved by using anti-BAFF and anti-APRIL detection antibodies along with HRP, all of which were loaded onto nanostructures composed of MoS2/multiwall carbon nanotubes (MoS2/MWCNTs), which enabled signal generation (through the hydroquinone/H2O2 system) and amplification [77]. An electrochemical immunosensor for the MS-associated protein biomarker chemokine (C-C motif) ligand 5 (CCL5) was developed. CCL5 was captured from biological samples through biotinylated anti-CCL5 antibodies (immobilized onto magnetic microparticles pre-functionalized with neutravidin) and subsequently detected with anti-CCL5 antibodies along with HRP-labeled secondary antibody (through the amperometric signal produced in the presence of H2O2 and using hydroquinone as the redox mediator) in a sandwich-assay setting [78]. One more electrochemical immunosensor has been developed that can serve simultaneous determination of the CXCL7 chemokine and the MMP3 enzyme/metalloproteinase, both of which are present at elevated levels in serum of RA patients. The sensor has been based on capture anti-CXCL7 and anti-MMP3 antibodies covalently immobilized on magnetic beads and on detection biotinylated anti-CXCL7 and anti-MMP3 antibodies along with HRP-streptavidin conjugates [79]. Some years earlier, an electrochemical immunosensor was developed for detecting TNFα, the well-known inflammatory protein biomarker; the sensor was based on a gold working electrode functionalized with anti-TNFα antibodies through covalent immobilization by means of sulfosuccinimidyl 6-(3′-(2-pyridyldithio) propionamido) hexanoate (sulfo-LC-SPDP) [80].
It should be noted that the term “immunosensor” is sometimes used in the literature to define a properly modified specific antibody recognizing/”sensing” a protein biomarker, such as TNF-α [81]; such antibodies (“quenchbodies”) can be used in various applications, e.g., in conventional immunoassays.
Table 2 has attempted to include most of the AD immunosensors reported to date that detect specific protein biomarkers, other than autoantibodies, and present their main characteristics.
Table 2. AD immunosensors that can detect protein biomarkers other than autoantibodies.
Type of Signal Transduction Immunoassay Principle Protein-Biomarker LoD/
Concentration Range		 Autoimmune Disease Biological Sample References
Optical
(Multi Area Reflectance Spectroscopy—MARS)		 Non-competitive, sandwich-type assay Procalcitonin and interleukin-6 (IL-6) 2.0 ng mL−1 (PCT) and 0.01 ng mL−1 (IL-6)/
up to 100.0 ng mL−1 (PCT) and
up to 10.0 ng mL−1 (IL-6)		 Various inflammatory/autoimmune diseases Human serum [74]
Electrochemical
(Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS))		 Non-competitive, direct-type assay Oncostatin-M receptor (sOSMR) protein 0.42 pg mL−1/
0.005–500 pg mL−1		 Systemic sclerosis (SSc) Serum from healthy individuals and SSc patients [41]
Electrochemical
(Amperometry)		 Non-competitive, sandwich-type assay B cell activation factor (BAFF) and a proliferation-induced ligand (APRIL) 0.33 pg mL−1 (BAFF) and 16.4 pg mL−1 (APRIL)
/
1.1–100 pg mL−1 (BAFF) and 0.05–20 ng mL−1 (APRIL)		 Systemic lupus erythematosus (SLE) Serum from healthy individuals and SLE patients [76]
Electrochemical
(Amperometry)		 Non-competitive, sandwich-type assay B cell activation factor (BAFF) and a proliferation-induced ligand (APRIL) 0.08 ng mL−1 (BAFF) and 0.06 ng mL−1 (APRIL)
/
0.24–120 ng mL−1 (BAFF) and 0.19–25 ng mL−1 (APRIL)		 SLE Serum from SLE patients [77]
Electrochemical
(Amperometry)		 Non-competitive, sandwich-type assay CCL5 chemokine 40 pg mL−1/
0.1–300 ng mL−1		 Multiple sclerosis (MS) Serum from healthy individuals and MS patients [78]
Electrochemical
(Amperometry)		 Non-competitive, sandwich-type assay IL-6 0.42 pg mL−1/
0.97–250 pg mL−1		 Rheumatoid arthritis (RA) Human serum (spiked) [22]
Electrochemical
(Amperometry)		 Non-competitive, sandwich-type assay CXCL7 chemokine and MMP3 metalloproteinase 0.8 ng mL−1 (CXCL7) and 1.2 pg mL−1 (MMP3)/
1–75 ng mL−1 (CXCL7) and 2.0–2000 pg mL−1 (MMP3)		 RA Serum from healthy individuals and RA patients [79]
Electrochemical
(EIS)		 Non-competitive, direct-type assay Tumor necrosis factor α (TNFα) 0.085 pg mL−1/
1–25 pg mL−1		 Various inflammatory/autoimmune diseases Serum and tears from healthy individuals; cerebrospinal fluid (CFS) from patients undergone routine lumbar puncture [80]
Electrochemical
(Differential pulse voltammetry (DPV) and EIS)		 Non-competitive, direct-type assay Myelin Basic Protein (MBP) and Tau proteins 0.30 nM (MBP) and 0.15 nM (Tau) MS CSF and serum from MS patients [82]
Electrochemical
(Voltammetry)		 Non-competitive, direct-type assay Insulin 5 pM/
5–200 pM		 Diabetes types I and II Serum from diabetic patients [83]
Electrochemical
(EIS)		 Non-competitive, direct-type assay Interleukin-12 (IL-12) 3.5 pg mL−1/
0.1–500 pg mL−1		 MS Fetal bovine serum (FBS) [84]
Electrochemical
(Amperometry)		 Non-competitive, direct-type assay Macrophage migration inhibitory factor (MIF) 0.02 ng mL−1/
0.03–230 ng mL−1		 RA Serum from RA patients [85]
Electrochemical
(EIS)		 Non-competitive, direct-type assay IL-12 <100 fM MS (Buffer) [86]
In addition to the inflammation/AD-related protein biomarkers shown in Table 2, a recent review article has presented various analytical assays for HMB1 [87]. HMB1 is a well-known multifunctional protein associated with severe inflammation storms and proposed as a prognostic biomarker for COVID-19; an electrochemical immunosensor prototype for detecting its levels in fluids [87].
In addition to the AD immunosensors, AD aptasensors have been developed for the detection of biomarkers, such as TNFα, various interleukins, and C-Reactive Protein [88][89]. In these AD aptasensors, the specific anti-analyte antibodies were replaced with specially designed and prepared binders, known as aptamers [90]. Moreover, sensors based on molecularly imprinted polymers have been reported in the literature, e.g., for the detection of insulin [91].

References

  1. Campuzano, S.; Pedrero, M.; González-Cortés, A.; Yáñez-Sedeño, P.; Pingarrón, J.M. Electrochemical biosensors for autoantibodies in autoimmune and cancer diseases. Anal. Methods 2019, 11, 871–887.
  2. Bieber, K.; Hundt, J.E.; Yu, X.; Ehlers, M.; Petersen, F.; Karsten, C.M.; Köhl, J.; Kridin, K.; Kalies, K.; Kasprick, A.; et al. Autoimmune pre-disease. Autoimmun. Rev. 2023, 22, 103236.
  3. Ghorbani, F.; Abbaszadeh, H.; Mehdizadeh, A.; Ebrahimi-Warkiani, M.; Rashidi, M.-R.; Yousefi, M. Biosensors and nanobiosensors for rapid detection of autoimmune diseases: A review. Microchim. Acta 2019, 186, 838.
  4. Quattrin, T.; Mastrandrea, L.D.; Walker, L.S.K. Type 1 diabetes. Lancet 2023, 401, 2149–2162.
  5. Smolen, J.S.; Aletaha, D.; McInnes, I.B. Rheumatoid arthritis. Lancet 2016, 388, 2023–2038, Erratum in Lancet 2016, 388, 1984.
  6. Koushki, K.; Shahbaz, S.K.; Keshavarz, M.; Bezsonov, E.E.; Sathyapalan, T.; Sahebkar, A. Gold Nanoparticles: Multifaceted Roles in the Management of Autoimmune Disorders. Biomolecules 2021, 11, 1289.
  7. Popescu, B.F.G.; Pirko, I.; Lucchinetti, C.F. Pathology of Multiple Sclerosis: Where do we stand? Contin. Lifelong Learn. Neurol. 2013, 19, 901–921.
  8. Takei, M.; Kitamura, N.; Nagasawa, Y.; Tsuzuki, H.; Iwata, M.; Nagatsuka, Y.; Nakamura, H.; Imai, K.; Fujiwara, S. Are Viral Infections Key Inducers of Autoimmune Diseases? Focus on Epstein–Barr Virus. Viruses 2022, 14, 1900.
  9. Soldan, S.S.; Lieberman, P.M. Epstein–Barr virus and multiple sclerosis. Nat. Rev. Genet. 2022, 21, 51–64.
  10. Sinnberg, T.; Lichtensteiger, C.; Ali, O.H.; Pop, O.T.; Jochum, A.-K.; Risch, L.; Brugger, S.D.; Velic, A.; Bomze, D.; Kohler, P.; et al. Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19. Am. J. Respir. Crit. Care Med. 2023, 207, 38–49.
  11. Votto, M.; Castagnoli, R.; Marseglia, G.L.; Licari, A.; Brambilla, I. COVID-19 and autoimmune diseases: Is there a connection? Curr. Opin. Allergy Clin. Immunol. 2023, 23, 185–192.
  12. Wang, E.Y.; Mao, T.; Klein, J.; Dai, Y.; Huck, J.D.; Jaycox, J.R.; Liu, F.; Zhou, T.; Israelow, B.; Wong, P.; et al. Diverse Functional Autoantibodies in Patients with COVID-19. medRxiv Prepr. Serv. Health Sci. 2021, 595, 283–288.
  13. Lou, H.; Ling, G.S.; Cao, X. Autoantibodies in systemic lupus erythematosus: From immunopathology to therapeutic target. J. Autoimmun. 2022, 132, 102861.
  14. Staruszkiewicz, M.; Pituch-Noworolska, A.; Skoczen, S. Uncommon types of autoantibodies—Detection and clinical associations. Autoimmun. Rev. 2023, 22, 103263.
  15. Ma, H.; Murphy, C.; Loscher, C.E.; O’kennedy, R. Autoantibodies—Enemies, and/or potential allies? Front. Immunol. 2022, 13, 953726.
  16. Yoganathan, K.; Stevenson, A.; Tahir, A.; Sadler, R.; Radunovic, A.; Malek, N. Bedside and laboratory diagnostic testing in myasthenia. J. Neurol. 2022, 269, 3372–3384.
  17. Sokolova, M.V.; Schett, G.; Steffen, U. Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings. Clin. Rev. Allergy Immunol. 2021, 63, 138–151.
  18. Zhou, B.; Yan, Y.; Xie, J.; Huang, H.; Wang, H.; Gopinath, S.C.; Anbu, P.; He, S.; Zhang, L. Immunosensing the rheumatoid arthritis biomarker through bifunctional aldehyde-amine linkers on an iron oxide nanoparticle seeded voltammetry sensor. Nanomater. Nanotechnol. 2022, 12, 18479804221085103.
  19. Haro, I.; Sanmartí, R.; Gómara, M.J. Implications of Post-Translational Modifications in Autoimmunity with Emphasis on Citrullination, Homocitrullination and Acetylation for the Pathogenesis, Diagnosis and Prognosis of Rheumatoid Arthritis. Int. J. Mol. Sci. 2022, 23, 15803.
  20. Kwon, O.C.; Park, M.-C.; Kim, Y.-G. Interleukin-32 as a biomarker in rheumatic diseases: A narrative review. Front. Immunol. 2023, 14, 1140373.
  21. Li, F.; Ai, W.; Ye, J.; Wang, C.; Yuan, S.; Xie, Y.; Mo, X.; Li, W.; He, Z.; Chen, Y.; et al. Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression. Clin. Rheumatol. 2022, 41, 2309–2317.
  22. Zhang, C.; Shi, D.; Li, X.; Yuan, J. Microfluidic electrochemical magnetoimmunosensor for ultrasensitive detection of interleukin-6 based on hybrid of AuNPs and graphene. Talanta 2021, 240, 123173.
  23. Khan, M.A.; Mujahid, M. Recent Advances in Electrochemical and Optical Biosensors Designed for Detection of Interleukin 6. Sensors 2020, 20, 646.
  24. Zhang, X.; Zambrano, A.; Lin, Z.-T.; Xing, Y.; Rippy, J.; Wu, T. Immunosensors for Biomarker Detection in Autoimmune Diseases. Arch. Immunol. Ther. Exp. 2016, 65, 111–121.
  25. Singh, V.; Krishnan, S. Electrochemical and surface plasmon insulin assays on clinical samples. Analyst 2018, 143, 1544–1555.
  26. Heydari, R.; Koohi, F.; Rasouli, M.; Rezaei, K.; Abbasgholinejad, E.; Bekeschus, S.; Doroudian, M. Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents. Vaccines 2023, 11, 687.
  27. Selmaj, K.W.; Mycko, M.P.; Furlan, R.; Rejdak, K. Fluid phase biomarkers in multiple sclerosis. Curr. Opin. Neurol. 2022, 35, 286–292.
  28. Pang, H.; Luo, S.; Xiao, Y.; Xia, Y.; Li, X.; Huang, G.; Xie, Z.; Zhou, Z. Emerging Roles of Exosomes in T1DM. Front. Immunol. 2020, 11, 593348.
  29. Liu, X.; Jiang, H. Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis. Sensors 2017, 17, 2805.
  30. Aydin, M.; Aydin, E.B.; Sezgintürk, M.K. Chapter One—Advances in immunosensor technology. In Advances in Clinical Chemistry; Makowski, G.S., Ed.; Elsevier: Amsterdam, The Netherlands, 2021; Volume 102, pp. 1–62.
  31. Karachaliou, C.-E.; Koukouvinos, G.; Goustouridis, D.; Raptis, I.; Kakabakos, S.; Livaniou, E.; Petrou, P. Recent Developments in the Field of Optical Immunosensors Focusing on a Label-Free, White Light Reflectance Spectroscopy-Based Immunosensing Platform. Sensors 2022, 22, 5114.
  32. Vasuki, S.; Varsha, V.; Mithra, R.; Dharshni, S.; Abinaya, R.; Dharshini, N.; Sivarajasekar, N. Thermal Biosensors and Their Applications. Am. Int. J. Res. Sci. Technol. Eng. Math 2019, 1, 262–264.
  33. Patil, A.V.P.; Chuang, Y.-S.; Li, C.; Wu, C.-C. Recent Advances in Electrochemical Immunosensors with Nanomaterial Assistance for Signal Amplification. Biosensors 2023, 13, 125.
  34. Ramesh, M.; Janani, R.; Deepa, C.; Rajeshkumar, L. Nanotechnology-Enabled Biosensors: A Review of Fundamentals, Design Principles, Materials, and Applications. Biosensors 2022, 13, 40.
  35. Kobeissy, F.H.; Gulbakan, B.; Alawieh, A.; Karam, P.; Zhang, Z.; Guingab-Cagmat, J.D.; Mondello, S.; Tan, W.; Anagli, J.; Wang, K.; et al. Post-Genomics Nanotechnology Is Gaining Momentum: Nanoproteomics and Applications in Life Sciences. OMICS A J. Integr. Biol. 2014, 18, 111–131.
  36. Florea, A.; Melinte, G.; Simon, I.; Cristea, C. Electrochemical Biosensors as Potential Diagnostic Devices for Autoimmune Diseases. Biosensors 2019, 9, 38.
  37. Serin, M.; Kara, P. Biosensing strategies (approaches) for diagnosis and monitoring of multiple sclerosis. Talanta 2023, 252, 123794.
  38. Demirdöğen, B.C. A literature review of biosensors for multiple sclerosis: Towards personalized medicine and point-of-care testing. Mult. Scler. Relat. Disord. 2021, 48, 102675.
  39. Guo, K. Advances in the detection of rheumatoid arthritis related biomarker by highly sensitive electrochemical sensors. Int. J. Electrochem. Sci. 2023, 18, 100060.
  40. Volkmann, E.R.; Andréasson, K.; Smith, V. Systemic sclerosis. Lancet 2023, 401, 304–318.
  41. Avelino, K.Y.; Silva-Junior, A.G.; Pitta, M.G.; Errachid, A.; Oliveira, M.D.; Andrade, C.A. Nanoimmunosensor for the electrochemical detection of oncostatin M receptor and monoclonal autoantibodies in systemic sclerosis. Talanta 2023, 256, 124285.
  42. Chinnadayyala, S.R.; Cho, S. Electrochemical Immunosensor for the Early Detection of Rheumatoid Arthritis Biomarker: Anti-Cyclic Citrullinated Peptide Antibody in Human Serum Based on Avidin-Biotin System. Sensors 2021, 21, 124.
  43. Ronco, P.; Debiec, H. Molecular Pathogenesis of Membranous Nephropathy. Annu. Rev. Pathol. Mech. Dis. 2020, 15, 287–313.
  44. Hampitak, P.; Jowitt, T.A.; Melendrez, D.; Fresquet, M.; Hamilton, P.; Iliut, M.; Nie, K.; Spencer, B.; Lennon, R.; Vijayaraghavan, A. A Point-of-Care Immunosensor Based on a Quartz Crystal Microbalance with Graphene Biointerface for Antibody Assay. ACS Sens. 2020, 5, 3520–3532.
  45. Milo, T.; Kohanim, Y.K.; Toledano, Y.; Alon, U. Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance. Trends Immunol. 2023, 44, 365–371.
  46. Orlov, A.; Pushkarev, A.; Znoyko, S.; Novichikhin, D.; Bragina, V.; Gorshkov, B.; Nikitin, P. Multiplex label-free biosensor for detection of autoantibodies in human serum: Tool for new kinetics-based diagnostics of autoimmune diseases. Biosens. Bioelectron. 2020, 159, 112187.
  47. Chinnadayyala, S.R.; Park, J.; Abbasi, M.A.; Cho, S. Label-free electrochemical impedimetric immunosensor for sensitive detection of IgM rheumatoid factor in human serum. Biosens. Bioelectron. 2019, 143, 111642.
  48. Veigas, B.; Matias, A.; Calmeiro, T.; Fortunato, E.; Fernandes, A.R.; Baptista, P.V. Antibody modified gold nanoparticles for fast colorimetric screening of rheumatoid arthritis. Analyst 2019, 144, 3613–3619.
  49. Catassi, C.; Verdu, E.F.; Bai, J.C.; Lionetti, E. Coeliac disease. Lancet 2022, 399, 2413–2426.
  50. Habtamu, H.B.; Not, T.; De Leo, L.; Longo, S.; Moretto, L.M.; Ugo, P. Electrochemical Immunosensor Based on Nanoelectrode Ensembles for the Serological Analysis of IgG-type Tissue Transglutaminase. Sensors 2019, 19, 1233.
  51. Hill, Q.A.; Hill, A.; Berentsen, S. Defining autoimmune hemolytic anemia: A systematic review of the terminology used for diagnosis and treatment. Blood Adv. 2019, 3, 1897–1906.
  52. Moraes, M.; Lima, L.R.; Vicentini-Oliveira, J.C.; De Souza, A.V.G.; Oliveira, O.N.; Deffune, E.; Ribeiro, S.J.L. Immunosensor for the Diagnostics of Autoimmune Hemolytic Anemia (AIHA) Based on Immobilization of a Monoclonal Antibody on a Layer of Silk Fibroin. J. Nanosci. Nanotechnol. 2019, 19, 3772–3776.
  53. Raos, M.; Lukic, M.; Pulanic, D.; Vodanovic, M.; Cepulic, B.G. The role of serological and molecular testing in the diagnostics and transfusion treatment of autoimmune haemolytic anaemia. Blood Transfus. Trasfus. Sangue 2022, 20, 319–328.
  54. Scurt, F.G.; Bose, K.; Hammoud, B.; Brandt, S.; Bernhardt, A.; Gross, C.; Mertens, P.R.; Chatzikyrkou, C. Old known and possible new biomarkers of ANCA-associated vasculitis. J. Autoimmun. 2022, 133, 102953.
  55. Yang, W.; Peng, Q.; Guo, Z.; Wu, H.; Ding, S.; Chen, Y.; Zhao, M. PtCo nanocubes/reduced graphene oxide hybrids and hybridization chain reaction-based dual amplified electrochemiluminescence immunosensing of antimyeloperoxidase. Biosens. Bioelectron. 2019, 142, 111548.
  56. Fagúndez, P.; Brañas, G.; Cairoli, E.; Laíz, J.; Tosar, J.P. An electrochemical biosensor for rapid detection of anti-dsDNA antibodies in absolute scale. Analyst 2018, 143, 3874–3882.
  57. Giannetto, M.; Bianchi, V.; Gentili, S.; Fortunati, S.; De Munari, I.; Careri, M. An integrated IoT-Wi-Fi board for remote data acquisition and sharing from innovative immunosensors. Case of study: Diagnosis of celiac disease. Sens. Actuators B Chem. 2018, 273, 1395–1403.
  58. Ma, X.; Fang, C.; Yan, J.; Zhao, Q.; Tu, Y. A label-free electrochemiluminescent immunosensor for glutamate decarboxylase antibody detection on AuNPs supporting interface. Talanta 2018, 186, 206–214.
  59. Nascimento, N.M.D.; Juste-Dolz, A.; Grau-García, E.; Román-Ivorra, J.A.; Puchades, R.; Maquieira, A.; Morais, S.; Gimenez-Romero, D. Label-free piezoelectric biosensor for prognosis and diagnosis of Systemic Lupus Erythematosus. Biosens. Bioelectron. 2017, 90, 166–173.
  60. Rosales-Rivera, L.C.; Dulay, S.; Lozano-Sánchez, P.; Katakis, I.; Acero-Sánchez, J.L.; O’sullivan, C.K. Disulfide-modified antigen for detection of celiac disease-associated anti-tissue transglutaminase autoantibodies. Anal. Bioanal. Chem. 2017, 409, 3799–3806.
  61. Giannetto, M.; Mattarozzi, M.; Umiltà, E.; Manfredi, A.; Quaglia, S.; Careri, M. 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. Biosens. Bioelectron. 2014, 62, 325–330.
  62. Derkus, B.; Emregul, E.; Yucesan, C.; Emregul, K.C. Myelin basic protein immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy. Biosens. Bioelectron. 2013, 46, 53–60.
  63. Neves, M.M.; González-García, M.B.; Nouws, H.P.; Costa-García, A. Celiac disease detection using a transglutaminase electrochemical immunosensor fabricated on nanohybrid screen-printed carbon electrodes. Biosens. Bioelectron. 2012, 31, 95–100.
  64. Dulay, S.; Lozano-Sánchez, P.; Iwuoha, E.; Katakis, I.; O’Sullivan, C.K. Electrochemical detection of celiac disease-related anti-tissue transglutaminase antibodies using thiol based surface chemistry. Biosens. Bioelectron. 2011, 26, 3852–3856.
  65. Villa, M.d.G.; Jiménez-Jorquera, C.; Haro, I.; Gomara, M.J.; Sanmartí, R.; Fernández-Sánchez, C.; Mendoza, E. Carbon nanotube composite peptide-based biosensors as putative diagnostic tools for rheumatoid arthritis. Biosens. Bioelectron. 2011, 27, 113–118.
  66. Drouvalakis, K.A.; Bangsaruntip, S.; Hueber, W.; Kozar, L.G.; Utz, P.J.; Dai, H. Peptide-coated nanotube-based biosensor for the detection of disease-specific autoantibodies in human serum. Biosens. Bioelectron. 2008, 23, 1413–1421.
  67. Balkenhohl, T.; Lisdat, F. Screen-printed electrodes as impedimetric immunosensors for the detection of anti-transglutaminase antibodies in human sera. Anal. Chim. Acta 2007, 597, 50–57.
  68. Fakhrullin, R.F.; Vinter, V.G.; Zamaleeva, A.I.; Matveeva, M.V.; Kourbanov, R.A.; Temesgen, B.K.; Ishmuchametova, D.G.; Abramova, Z.I.; Konovalova, O.A.; Salakhov, M.K. Quartz crystal microbalance immunosensor for the detection of antibodies to double-stranded DNA. Anal. Bioanal. Chem. 2007, 388, 367–375.
  69. Choi, S.H.; Lee, J.W.; Sim, S.J. Enhanced performance of a surface plasmon resonance immunosensor for detecting Ab–GAD antibody based on the modified self-assembled monolayers. Biosens. Bioelectron. 2005, 21, 378–383.
  70. Ortiz, M.; Wajs, E.M.; Fragoso, A.; O’Sullivan, C.K. A bienzymatic amperometric immunosensor exploiting supramolecular construction for ultrasensitive protein detection. Chem. Commun. 2012, 48, 1045–1047.
  71. Rosales-Rivera, L.; Acero-Sánchez, J.; Lozano-Sánchez, P.; Katakis, I.; O’Sullivan, C. Electrochemical immunosensor detection of antigliadin antibodies from real human serum. Biosens. Bioelectron. 2011, 26, 4471–4476.
  72. Balkenhohl, T.; Lisdat, F. An impedimetric immunosensor for the detection of autoantibodies directed against gliadins. Analyst 2007, 132, 314–322.
  73. Adeniyi, O.K.; Ngqinambi, A.; Mashazi, P.N. Ultrasensitive detection of anti-p53 autoantibodies based on nanomagnetic capture and separation with fluorescent sensing nanobioprobe for signal amplification. Biosens. Bioelectron. 2020, 170, 112640.
  74. Tsounidi, D.; Tsaousis, V.; Xenos, N.; Kroupis, C.; Moutsatsou, P.; Christianidis, V.; Goustouridis, D.; Raptis, I.; Kakabakos, S.; Petrou, P. Simultaneous determination of procalcitonin and interleukin-6 in human serum samples with a point-of-care biosensing device. Talanta 2023, 258, 124403.
  75. Akhil, A.; Bansal, R.; Anupam, K.; Tandon, A.; Bhatnagar, A. Systemic lupus erythematosus: Latest insight into etiopathogenesis. Rheumatol. Int. 2023, 43, 1381–1393.
  76. Arévalo, B.; Blázquez-García, M.; Valverde, A.; Serafín, V.; Montero-Calle, A.; Solís-Fernández, G.; Barderas, R.; Yáñez-Sedeño, P.; Campuzano, S.; Pingarrón, J. Simultaneous electrochemical immunosensing of relevant cytokines to diagnose and track cancer and autoimmune diseases. Bioelectrochemistry 2022, 146, 108157.
  77. Arévalo, B.; Blázquez-García, M.; Valverde, A.; Serafín, V.; Montero-Calle, A.; Solís-Fernández, G.; Barderas, R.; Campuzano, S.; Yáñez-Sedeño, P.; Pingarrón, J.M. Binary MoS2 nanostructures as nanocarriers for amplification in multiplexed electrochemical immunosensing: Simultaneous determination of B cell activation factor and proliferation-induced signal immunity-related cytokines. Microchim. Acta 2022, 189, 143.
  78. Guerrero, S.; Sánchez-Tirado, E.; Agüí, L.; González-Cortés, A.; Yáñez-Sedeño, P.; Pingarrón, J.M. Development of an Electrochemical CCL5 Chemokine Immunoplatform for Rapid Diagnosis of Multiple Sclerosis. Biosensors 2022, 12, 610.
  79. Guerrero, S.; Sánchez-Tirado, E.; Agüí, L.; González-Cortés, A.; Yáñez-Sedeño, P.; Pingarrón, J. Simultaneous determination of CXCL7 chemokine and MMP3 metalloproteinase as biomarkers for rheumatoid arthritis. Talanta 2021, 234, 122705.
  80. Cruz, A.; Queirós, R.; Abreu, C.M.; Barata, C.; Fernandes, R.; Silva, R.; Ambrósio, A.F.; Soares-Dos-Reis, R.; Guimarães, J.; Sá, M.J.; et al. Electrochemical Immunosensor for TNFα-Mediated Inflammatory Disease Screening. ACS Chem. Neurosci. 2019, 10, 2676–2682.
  81. Li, H.; Li, X.; Chen, L.; Li, B.; Dong, H.; Liu, H.; Yang, X.; Ueda, H.; Dong, J. Quench-Release-Based Fluorescent Immunosensor for the Rapid Detection of Tumor Necrosis Factor α. ACS Omega 2021, 6, 31009–31016.
  82. Derkus, B.; Bozkurt, P.A.; Tulu, M.; Emregul, K.C.; Yucesan, C.; Emregul, E. Simultaneous quantification of Myelin Basic Protein and Tau proteins in cerebrospinal fluid and serum of Multiple Sclerosis patients using nanoimmunosensor. Biosens. Bioelectron. 2017, 89, 781–788.
  83. Singh, V.; Krishnan, S. Voltammetric Immunosensor Assembled on Carbon-Pyrenyl Nanostructures for Clinical Diagnosis of Type of Diabetes. Anal. Chem. 2015, 87, 2648–2654.
  84. Bhavsar, K.; Fairchild, A.; Alonas, E.; Bishop, D.K.; La Belle, J.T.; Sweeney, J.; Alford, T.; Joshi, L. A cytokine immunosensor for Multiple Sclerosis detection based upon label-free electrochemical impedance spectroscopy using electroplated printed circuit board electrodes. Biosens. Bioelectron. 2009, 25, 506–509.
  85. Li, S.; Zhang, R.; Li, P.; Yi, W.; Zhang, Z.; Chen, S.; Su, S.; Zhao, L.; Hu, C. Development of a novel method to measure macrophage migration inhibitory factor (MIF) in sera of patients with rheumatoid arthritis by combined electrochemical immunosensor. Int. Immunopharmacol. 2008, 8, 859–865.
  86. La Belle, J.T.; Bhavsar, K.; Fairchild, A.; Das, A.; Sweeney, J.; Alford, T.; Wang, J.; Bhavanandan, V.P.; Joshi, L. A cytokine immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy. Biosens. Bioelectron. 2007, 23, 428–431.
  87. Štros, M.; Polanská, E.V.; Hlaváčová, T.; Skládal, P. Progress in Assays of HMGB1 Levels in Human Plasma—The Potential Prognostic Value in COVID-19. Biomolecules 2022, 12, 544.
  88. Shatunova, E.A.; Korolev, M.A.; Omelchenko, V.O.; Kurochkina, Y.D.; Davydova, A.S.; Venyaminova, A.G.; Vorobyeva, M.A. Aptamers for Proteins Associated with Rheumatic Diseases: Progress, Challenges, and Prospects of Diagnostic and Therapeutic Applications. Biomedicines 2020, 8, 527.
  89. Jo, H.; Kim, S.-K.; Youn, H.; Lee, H.; Lee, K.; Jeong, J.; Mok, J.; Kim, S.-H.; Park, H.-S.; Ban, C. A highly sensitive and selective impedimetric aptasensor for interleukin-17 receptor A. Biosens. Bioelectron. 2016, 81, 80–86.
  90. Blind, M.; Blank, M. Aptamer Selection Technology and Recent Advances. Mol. Ther. Nucleic Acids 2015, 4, e223.
  91. Zhao, C.-J.; Ma, X.-H.; Li, J.-P. An Insulin Molecularly Imprinted Electrochemical Sensor Based on Epitope Imprinting. Chin. J. Anal. Chem. 2017, 45, 1360–1366.
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Chrysoula-Evangelia Karachaliou
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