Special Issue "Antibody-Based Diagnostics"

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (30 April 2019)

Special Issue Editors

Guest Editor
Prof. Gunnar Houen

Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark
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Phone: +4532683276
Guest Editor
Dr. Nicole Hartwig Trier

Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark
Website | E-Mail

Special Issue Information

Dear Colleagues,

Antibodies are an important and vital constituent of adaptive immunity, with the potential to recognize an essentially unlimited set of foreign molecules (antigens). Antibodies are rapidly made in response to infections and, therefore, they have immense diagnostic value. Moreover, since Abs undergo affinity maturation and class/isotype switching in the course of infections, the Ab distribution can be used to distinguish between acute and chronic infections.

Besides infections, many diseases are characterized by specific Ab productions. In autoimmune diseases, Abs recognizing autoantigens (autoantibodies) are found in varying frequencies and have immense diagnostic value, although their pathophysiological role is uncertain. In allergic diseases Abs (IgE) have both diagnostic value and are the direct cause of disease, for which reason IgE neutralizing therapies are very successful. Some malignant and more benign lymphoproliferative diseases are characterized by production of monoclonal Abs or Ab fragments (M components), which have immense diagnostic value. In rare cases, cancers may also give rise to production of autoantibodies, which can be used diagnostically.

Finally, due to their specificity and versatility, tailor-made Abs, mainly in the form of monoclonal Abs, can be used diagnostically for measurement of a wide range of analytes/targets, most often in the form of sandwich immunoassays, immunocytochemistry/immunohistochemistry and flow-based cell assays. Such assays are continuously being refined and combined with other techniques, e.g. mass spectrometry, PCR, etc., making Ab-based diagnostics the most important technique in many areas of bio-medicine.

This Special Issue on antibody-based diagnostics aims to describe current state-of-the-art techniques and applications, as well as newer and emerging uses of antibodies in diagnostics.

Prof. Gunnar Houen
Dr. Nicole Hartwig Trier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 350 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibodies
  • Autoantibodies
  • Autoimmune diseases
  • Infections
  • Allergy
  • Cancer
  • Monoclonal antibodies
  • Peptide antibodies
  • Lymphoproliferative diseases
  • Immunoassays
  • Immunocytochemistry
  • Immunohistochemistry

Published Papers (7 papers)

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Research

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Open AccessArticle
Specificity of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis
Antibodies 2019, 8(2), 37; https://doi.org/10.3390/antib8020037
Received: 23 April 2019 / Revised: 28 May 2019 / Accepted: 6 June 2019 / Published: 7 June 2019
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Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, [...] Read more.
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, we analyzed the reactivity of RA sera to several post-translationally modified epitopes, in order to further characterize the specific nature of ACPAs by immunoassays. Substituting citrulline with other amino acids, e.g., D-citrulline, homo-citrulline and methyl-arginine illustrated that ACPAs are utmost specific for citrullinated targets. Collectively, these findings support that ACPAs and citrullinated targets are specific for RA, making citrulline-containing peptide targets the most effective assays for detection of ACPAs. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
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Open AccessArticle
EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls
Antibodies 2019, 8(2), 35; https://doi.org/10.3390/antib8020035
Received: 30 April 2019 / Revised: 24 May 2019 / Accepted: 28 May 2019 / Published: 1 June 2019
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Abstract
Epstein–Barr Virus (EBV) has been associated with development of rheumatic connective tissue diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in genetically susceptible individuals. Diagnosis of RA and SLE relies on clinical criteria in combination with the presence of characteristic autoantibodies. [...] Read more.
Epstein–Barr Virus (EBV) has been associated with development of rheumatic connective tissue diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in genetically susceptible individuals. Diagnosis of RA and SLE relies on clinical criteria in combination with the presence of characteristic autoantibodies. In addition, antibodies to several EBV antigens have been shown to be elevated in patients with these diseases compared to healthy controls (HC). Here, we elaborated improved enzyme-linked immunosorbent assays for antibodies (IgM, IgA, IgG) to the EBV proteins Epstein-Barr Virus nuclear antigen (EBNA)1 and early antigen diffuse (EAD) in order to determine their potential diagnostic role. We showed that especially EBNA1 IgM distinguished RA from SLE and HCs and also distinguished SLE from HCs. EBNA1 IgA was almost as effective in differentiating RA from SLE and HC, while EAD IgG and IgA were able to discern SLE patients from RA patients and HCs. Collectively, these findings illustrate the potential diagnostic use of antibodies to EBV proteins to diagnose RA and to differentiate SLE from RA. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
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Open AccessArticle
Kinetic Analysis and Epitope Mapping of Monoclonal Antibodies to Salmonella Typhimurium Flagellin Using a Surface Plasmon Resonance Biosensor
Antibodies 2019, 8(1), 22; https://doi.org/10.3390/antib8010022
Received: 11 February 2019 / Revised: 28 February 2019 / Accepted: 2 March 2019 / Published: 6 March 2019
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Abstract
Salmonella Typhimurium is one of the leading causes of foodborne diseases worldwide. Biosensors and immunoassays utilizing monoclonal antibodies are widely used for the detection and subtyping of S. Typhimurium. However, due to insufficient information on the nature of binding with S. Typhimurium flagellin, [...] Read more.
Salmonella Typhimurium is one of the leading causes of foodborne diseases worldwide. Biosensors and immunoassays utilizing monoclonal antibodies are widely used for the detection and subtyping of S. Typhimurium. However, due to insufficient information on the nature of binding with S. Typhimurium flagellin, the selection of appropriate antibodies for assay development is a cumbersome task. Hence, we aimed to compare the binding kinetics of a panel of monoclonal antibodies and their relative binding sites to flagellin antigen using a surface plasmon resonance biosensor. Initially, the flagellin was captured on the sensor surface through an immobilized anti-flagellin antibody. The interactions of different concentrations of monoclonal antibodies to flagellin were determined, and binding curves were fitted using 1:1 bio-interaction model to calculate the kinetic parameters. For epitope mapping, pairwise comparisons were completed to determine the binding inhibition of each paired combination of monoclonal antibodies. It was found that these monoclonal antibodies differed significantly (p < 0.05) in association rate, dissociation rate, and equilibrium dissociation constants. Of the five monoclonal antibodies, only two interfered with the binding of each other. Four distinct epitopes located within a 23 kDa domain of flagellin were identified. Findings from this study provide crucial information needed for the further development and optimization of biosensors and other immunoassays for the detection and subtyping of Salmonella. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
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Open AccessArticle
Evaluation of the NovaLisa™ Leishmania Infantum IgG ELISA in A Reference Diagnostic Laboratory in A Non-Endemic Country
Antibodies 2019, 8(1), 20; https://doi.org/10.3390/antib8010020
Received: 7 February 2019 / Revised: 22 February 2019 / Accepted: 23 February 2019 / Published: 27 February 2019
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Abstract
Anti-Leishmania antibodies may be detectable in patients with leishmaniasis. Here, we compared a commercial enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Leishmania antibodies, with an immunofluorescence antibody test (IFAT) that is no longer commercially available. Eighty-six serum samples from 73 [...] Read more.
Anti-Leishmania antibodies may be detectable in patients with leishmaniasis. Here, we compared a commercial enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Leishmania antibodies, with an immunofluorescence antibody test (IFAT) that is no longer commercially available. Eighty-six serum samples from 73 patients were tested. The results obtained by the NovaLisa™ Leishmania infantum IgG ELISA, interpreted according to the instructions of the manufacturer, but with a modified cut-off for borderline positive values, were compared with the IFAT results that were already available. Moreover, Leishmania Western blot IgG results were available for 43 of the samples. The overall concordance of ELISA and IFAT was 67%. The ELISA and IFAT tests scored as 24% and 15% of the samples being positive, respectively, while 13% and 33% scored as borderline-positive, respectively. Using a Western blot (WB) as the reference, the sensitivities and specificities for the positive plus borderline-positive samples combined was 95.5% (95% confidence interval (CI), 77.2–99.9%) and 81.0% (95% CI, 58.1–94.6%) for ELISA, and 95.5% (95% CI, 77.2–99.9%) and 42.9% (95% CI, 21.8–66.0%) for IFAT, respectively. Overall, the ELISA proved to be a cost-effective alternative to the IFAT, due to its higher accuracy and specificity, and with a consequently lower number of confirmatory WB tests being required. Lastly, we also present data on the associations between seroconversion and the type of leishmaniasis. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)

Review

Jump to: Research

Open AccessReview
Ion Channel Targeting with Antibodies and Antibody Fragments for Cancer Diagnosis
Antibodies 2019, 8(2), 33; https://doi.org/10.3390/antib8020033
Received: 21 March 2019 / Revised: 17 May 2019 / Accepted: 20 May 2019 / Published: 24 May 2019
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Abstract
The antibody era has greatly impacted cancer management in recent decades. Indeed, antibodies are currently applied for both cancer diagnosis and therapy. For example, monoclonal antibodies are the main constituents of several in vitro diagnostics, which are applied at many levels of cancer [...] Read more.
The antibody era has greatly impacted cancer management in recent decades. Indeed, antibodies are currently applied for both cancer diagnosis and therapy. For example, monoclonal antibodies are the main constituents of several in vitro diagnostics, which are applied at many levels of cancer diagnosis. Moreover, the great improvement provided by in vivo imaging, especially for early-stage cancer diagnosis, has traced the path for the development of a complete new class of antibodies, i.e., engineered antibody fragments. The latter embody the optimal characteristics (e.g., low renal retention, rapid clearance, and small size) which make them ideal for in vivo applications. Furthermore, the present review focuses on reviewing the main applications of antibodies and antibody fragments for solid cancer diagnosis, both in vitro and in vivo. Furthermore, we review the scientific evidence showing that ion channels represent an almost unexplored class of ideal targets for both in vitro and in vivo diagnostic purposes. In particular, we review the applications, in solid cancers, of monoclonal antibodies and engineered antibody fragments targeting the voltage-dependent ion channel Kv 11.1, also known as hERG1. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
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Open AccessReview
The Diagnostic and Clinical Utility of Autoantibodies in Systemic Vasculitis
Antibodies 2019, 8(2), 31; https://doi.org/10.3390/antib8020031
Received: 18 March 2019 / Revised: 14 April 2019 / Accepted: 16 April 2019 / Published: 1 May 2019
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Abstract
Considerable progress has been made in understanding the role of autoantibodies in systemic vasculitides (SV), and consequently testing for anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane antibodies (anti-GBM), and anti-C1q antibodies is helpful and necessary in the diagnosis, prognosis, and monitoring of small-vessel [...] Read more.
Considerable progress has been made in understanding the role of autoantibodies in systemic vasculitides (SV), and consequently testing for anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane antibodies (anti-GBM), and anti-C1q antibodies is helpful and necessary in the diagnosis, prognosis, and monitoring of small-vessel vasculitis. ANCA-directed proteinase 3 (PR3-) or myeloperoxidase (MPO-) are sensitive and specific serologic markers for ANCA-associated vasculitides (AAV), anti-GBM antibodies are highly specific for the patients with anti-GBM antibody disease (formerly Goodpasture’s syndrome), and autoantibodies to C1q are characteristic of hypocomlementemic urticarial vasculitis syndrome (HUVS; anti-C1q vasculitis). The results of a current EUVAS study have led to changes in the established strategy for the ANCA testing in small-vessel vasculitis. The revised 2017 international consensus recommendations for ANCA detection support the primary use PR3- and MPO-ANCA immunoassays without the categorical need for additional indirect immunofluorescence (IIF). Interestingly, the presence of PR3- and MPO-ANCA have led to the differentiation of distinct disease phenotype of AAV: PR3-ANCA-associated vasculitis (PR3-AAV), MPO-ANCA-associated vasculitis (MPO-AAV), and ANCA-negative vasculitis. Further studies on the role of these autoantibodies are required to better categorize and manage appropriately the patients with small-vessel vasculitis and to develop more targeted therapy. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
Open AccessReview
Peptides for Infectious Diseases: From Probe Design to Diagnostic Microarrays
Antibodies 2019, 8(1), 23; https://doi.org/10.3390/antib8010023
Received: 13 February 2019 / Revised: 28 February 2019 / Accepted: 4 March 2019 / Published: 12 March 2019
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Abstract
Peptides and peptidomimetics have attracted revived interest regarding their applications in chemical biology over the last few years. Their chemical versatility, synthetic accessibility and the ease of storage and management compared to full proteins have made peptides particularly interesting in diagnostic applications, where [...] Read more.
Peptides and peptidomimetics have attracted revived interest regarding their applications in chemical biology over the last few years. Their chemical versatility, synthetic accessibility and the ease of storage and management compared to full proteins have made peptides particularly interesting in diagnostic applications, where they proved to efficiently recapitulate the molecular recognition properties of larger protein antigens, and were proven to be able to capture antibodies circulating in the plasma and serum of patients previously exposed to bacterial or viral infections. Here, we describe the development, integration and application of strategies for computational prediction and design, advanced chemical synthesis, and diagnostic deployment in multiplexed assays of peptide-based materials which are able to bind antibodies of diagnostic as well as therapeutic interest. By presenting successful applications of such an integrated strategy, we argue that they will have an ever-increasing role in both basic and clinical realms of research, where important advances can be expected in the next few years. Full article
(This article belongs to the Special Issue Antibody-Based Diagnostics)
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