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Discovery of Antibody Biomarker
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Discovery of Antibody Biomarker

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 31704

Special Issue Editor

Dr. Takaki Hiwasa

E-Mail Website
Guest Editor
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Interests: SEREX; immunome; cancer; atherosclerosis; cerebro- and cardiovascular disease; oncogene; protease; signal transduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers are important and indispensable not only for diagnosis but also for the identification of therapeutic targets. Thus far, many antigen, enzyme, and nucleic acid markers have been developed, yet only few antibody markers are known. Autoantibodies have causal roles in autoimmune diseases, and may affect the development of cancer. Until recently, it was believed that autoantibodies appeared only in patients with autoimmune disease or cancer. However, the recent development of technology has revealed that autoantibodies are developed against most proteins in the body. Such autoantibodies may reflect an individual’s medical history. Therefore, autoantibodies can be applicable for diagnosis of other varieties of diseases in addition to autoimmune disease and cancer. Antibody levels are tremendously increased by repeated exposure to antigens. Therefore, antibody markers are highly sensitive and capable of discriminate trivial alterations of cells and organs. It has been suggested that autoantibodies sometimes play causal roles in other diseases than autoimmune diseases. Thus, analysis of autoantibodies is effective in the identification of therapeutic targets. Remarkable development of antibody biomarkers is expected in the future.

Dr. Takaki Hiwasa
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 submissions that pass pre-check are 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • autoantibody biomarker
  • antibody technology
  • autoimmune disease
  • cancer immunology
  • neuroimmunology
  • diabetes mellitus
  • cardiovascular disease
  • atherosclerosis

Published Papers (7 papers)

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Research

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11 pages, 1573 KiB  
Article
Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength
by Christian Schwiebert, Peter Kühnen, Niels-Peter Becker, Tim Welsink, Theresa Keller, Waldemar B. Minich, Susanna Wiegand and Lutz Schomburg
Int. J. Mol. Sci. 2020, 21(2), 463; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020463 - 11 Jan 2020
Cited by 10 | Viewed by 2427
Abstract
Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves’ ophthalmopathy. Other physiological roles of natural IGF1R-aAb are not known. We hypothesized that IGF1R-aAb may be related to muscle development. Serum samples (n = 408) from young overweight [...] Read more.
Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves’ ophthalmopathy. Other physiological roles of natural IGF1R-aAb are not known. We hypothesized that IGF1R-aAb may be related to muscle development. Serum samples (n = 408) from young overweight subjects (n = 143) were collected during a lifestyle intervention study. Anthropometric parameters, along with leptin, IGF1 and IGF1R-aAb concentrations, were analyzed, and the subjects were categorized into positive or negative for IGF1R-aAb. Eleven out of 143 subjects (7.7%) were positive for IGF1R-aAb. Identified IGF1R-aAb were molecularly characterized and showed antagonistic activity in vitro impairing IGF1-mediated IGF1R activation. Mean body weight, height or age were similar between IGF1R-aAb-positive and -negative subjects, but IGF1 concentrations differed. Jumping ability, as well as right and left handgrip strengths, were lower in the IGF1R-aAb-positive as compared to the IGF1R-aAb-negative subjects. We conclude that natural IGF1R-aAb are detectable in apparently healthy subjects and are capable of antagonizing IGF1-dependent IGF1R activation. Moreover, the presence of IGF1R-aAb is associated with poor physical strength. Although the causality of this association is unclear, the data imply a potential influence of IGF1R autoimmunity on muscle development. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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Review

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15 pages, 405 KiB  
Review
Significance of Autoantibodies in Autoimmune Encephalitis in Relation to Antigen Localization: An Outline of Frequently Reported Autoantibodies with a Non-Systematic Review
by Keiko Tanaka, Meiko Kawamura, Kenji Sakimura and Nobuo Kato
Int. J. Mol. Sci. 2020, 21(14), 4941; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144941 - 13 Jul 2020
Cited by 16 | Viewed by 3192
Abstract
Autoantibodies related to central nervous system (CNS) diseases propel research on paraneoplastic neurological syndrome (PNS). This syndrome develops autoantibodies in combination with certain neurological syndromes and cancers, such as anti-HuD antibodies in encephalomyelitis with small cell lung cancer and anti-Yo antibodies in cerebellar [...] Read more.
Autoantibodies related to central nervous system (CNS) diseases propel research on paraneoplastic neurological syndrome (PNS). This syndrome develops autoantibodies in combination with certain neurological syndromes and cancers, such as anti-HuD antibodies in encephalomyelitis with small cell lung cancer and anti-Yo antibodies in cerebellar degeneration with gynecological cancer. These autoantibodies have roles in the diagnosis of neurological diseases and early detection of cancers that are usually occult. Most of these autoantibodies have no pathogenic roles in neuronal dysfunction directly. Instead, antigen-specific cytotoxic T lymphocytes are thought to have direct roles in neuronal damage. The recent discoveries of autoantibodies against neuronal synaptic receptors/channels produced in patients with autoimmune encephalomyelitis have highlighted insights into our understanding of the variable neurological symptoms in this disease. It has also improved our understanding of intractable epilepsy, atypical psychosis, and some demyelinating diseases that are ameliorated with immune therapies. The production and motility of these antibodies through the blood-brain barrier into the CNS remains unknown. Most of these recently identified autoantibodies bind to neuronal and glial cell surface synaptic receptors, potentially altering the synaptic signaling process. The clinical features differ among pathologies based on antibody targets. The investigation of these antibodies provides a deeper understanding of the background of neurological symptoms in addition to novel insights into their basic neuroscience. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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26 pages, 801 KiB  
Review
Autoantibody Biomarkers in Rheumatic Diseases
by Eun Ha Kang, You-Jung Ha and Yun Jong Lee
Int. J. Mol. Sci. 2020, 21(4), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041382 - 18 Feb 2020
Cited by 20 | Viewed by 6366
Abstract
Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes, prognosis, and treatment decision-making. Furthermore, evidence has accumulated regarding the active involvement of disease-specific or disease-associated autoantibodies in the pathogenic process beyond [...] Read more.
Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes, prognosis, and treatment decision-making. Furthermore, evidence has accumulated regarding the active involvement of disease-specific or disease-associated autoantibodies in the pathogenic process beyond simple association with the disease, and such knowledge has become essential for us to better understand the clinical value of autoantibodies as a biomarker. This review will focus on the current update on the autoantibodies of four rheumatic diseases (rheumatoid arthritis, myositis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody associated vasculitis) where there has been a tremendous progress in our understanding on their biological effects and clinical use. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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15 pages, 915 KiB  
Review
Ganglionic Acetylcholine Receptor Antibodies and Autonomic Dysfunction in Autoimmune Rheumatic Diseases
by Michie Imamura, Akihiro Mukaino, Koutaro Takamatsu, Hiroto Tsuboi, Osamu Higuchi, Hideki Nakamura, Saori Abe, Yukio Ando, Hidenori Matsuo, Tadashi Nakamura, Takayuki Sumida, Atsushi Kawakami and Shunya Nakane
Int. J. Mol. Sci. 2020, 21(4), 1332; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041332 - 16 Feb 2020
Cited by 11 | Viewed by 5573
Abstract
Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren’s syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired [...] Read more.
Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren’s syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder, which causes dysautonomia that is mediated by autoantibodies against ganglionic acetylcholine receptors (gAChRs). The purpose of this review was to describe the characteristics of autonomic disturbance through previous case reports and the functional tests used in these studies and address the importance of anti-gAChR antibodies. We have established luciferase immunoprecipitation systems to detect antibodies against gAChR in the past and determined the prevalence of gAChR antibodies in various autoimmune diseases including AAG and rheumatic diseases. Autonomic dysfunction, which affects lower parasympathetic and higher sympathetic activity, is usually observed in ARD. The anti-gAChR antibodies may play a crucial role in autonomic dysfunction observed in ARD. Further studies are necessary to determine whether anti-gAChR antibody levels are correlated with the severity of autonomic dysfunction in ARD. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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14 pages, 810 KiB  
Review
Natural Autoantibodies in Chronic Pulmonary Diseases
by Kiyoharu Fukushima, Kazuyuki Tsujino, Shinji Futami and Hiroshi Kida
Int. J. Mol. Sci. 2020, 21(3), 1138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031138 - 08 Feb 2020
Cited by 7 | Viewed by 3623
Abstract
In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. [...] Read more.
In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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17 pages, 4274 KiB  
Review
Recent Developments of Electrochemical and Optical Biosensors for Antibody Detection
by Wei Xu, Daniel Wang, Derek Li and Chung Chiun Liu
Int. J. Mol. Sci. 2020, 21(1), 134; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010134 - 24 Dec 2019
Cited by 29 | Viewed by 6420
Abstract
Detection of biomarkers has raised much interest recently due to the need for disease diagnosis and personalized medicine in future point-of-care systems. Among various biomarkers, antibodies are an important type of detection target due to their potential for indicating disease progression stage and [...] Read more.
Detection of biomarkers has raised much interest recently due to the need for disease diagnosis and personalized medicine in future point-of-care systems. Among various biomarkers, antibodies are an important type of detection target due to their potential for indicating disease progression stage and the efficiency of therapeutic antibody drug treatment. In this review, electrochemical and optical detection of antibodies are discussed. Specifically, creating a non-label and reagent-free sensing platform and construction of an anti-fouling electrochemical surface for electrochemical detection are suggested. For optical transduction, a rapid and programmable platform for antibody detection using a DNA-based beacon is suggested as well as the use of bioluminescence resonance energy transfer (BRET) switch for low cost antibody detection. These sensing strategies have demonstrated their potential for resolving current challenges in antibody detection such as high selectivity, low operation cost, simple detection procedures, rapid detection, and low-fouling detection. This review provides a general update for recent developments in antibody detection strategies and potential solutions for future clinical point-of-care systems. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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16 pages, 1051 KiB  
Review
Relevance of Surface Neuronal Protein Autoantibodies as Biomarkers in Seizure-Associated Disorders
by Gabriela Dumitrita Stanciu, Veronica Bild, Daniela Carmen Ababei, Razvan Nicolae Rusu, Sorin Ioan Beschea Chiriac, Elena Rezuş and Andrei Luca
Int. J. Mol. Sci. 2019, 20(18), 4529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184529 - 13 Sep 2019
Cited by 6 | Viewed by 3497
Abstract
The detection of neuronal surface protein autoantibody-related disorders has contributed to several changes in our understanding of central nervous system autoimmunity. The clinical presentation of these disorders may be associated (or not) with tumors, and often patients develop an inexplicable onset of epilepsy, [...] Read more.
The detection of neuronal surface protein autoantibody-related disorders has contributed to several changes in our understanding of central nervous system autoimmunity. The clinical presentation of these disorders may be associated (or not) with tumors, and often patients develop an inexplicable onset of epilepsy, catatonic or autistic features, or memory and cognitive dysfunctions. The autoantigens in such cases have critical roles in synaptic transmission and plasticity, memory function, and process learning. For months, patients with such antibodies may be comatose or encephalopathic and yet completely recover with palliative care and immunotherapies. This paper reviews several targets of neuronal antibodies as biomarkers in seizure disorders, focusing mainly on autoantibodies, which target the extracellular domains of membrane proteins, namely leucine-rich glioma-inactivated-1 (LGI1), contactin-associated protein-like 2 (CASPR2), the N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid receptor-B (GABABR), the glycine receptor (GlyR), and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). In order to restore health status, limit hospitalization, and optimize results, testing these antibodies should be done locally, using internationally certified procedures for a precise and rapid diagnosis, with the possibility of initiating therapy as soon as possible. Full article
(This article belongs to the Special Issue Discovery of Antibody Biomarker)
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