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Antibodies, Volume 12, Issue 1 (March 2023) – 25 articles

Cover Story (view full-size image): Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. View this paper
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19 pages, 1303 KiB  
Review
New Insights into Pathogenesis and Treatment of ANCA-Associated Vasculitis: Autoantibodies and Beyond
by Marino Paroli, Chiara Gioia and Daniele Accapezzato
Antibodies 2023, 12(1), 25; https://doi.org/10.3390/antib12010025 - 21 Mar 2023
Cited by 4 | Viewed by 6444
Abstract
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare systemic diseases affecting small-caliber vessels. The damage caused by AAV mainly involves the lung and kidneys. AAV includes three different types: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis [...] Read more.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare systemic diseases affecting small-caliber vessels. The damage caused by AAV mainly involves the lung and kidneys. AAV includes three different types: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Although the different phenotypic forms of AAV share common features, recent studies have shown that there are significant differences in terms of pathogenetic mechanisms involving both the adaptive and innate immune systems. Advances in our understanding of pathogenesis have enabled the development of immuno-targeted therapies. This review illustrates the characteristics of the various forms of AAV and the new therapies available for this disease that can have lethal consequences if left untreated. Full article
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13 pages, 2577 KiB  
Review
Intracellular Antibodies for Drug Discovery and as Drugs of the Future
by T. H. Rabbitts
Antibodies 2023, 12(1), 24; https://doi.org/10.3390/antib12010024 - 16 Mar 2023
Cited by 2 | Viewed by 3720
Abstract
The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as engineered molecules that can be fused to moieties (referred [...] Read more.
The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as engineered molecules that can be fused to moieties (referred to as warheads) to replace the Fc effector region of a whole immunoglobulin to elicit intracellular responses, such as cell death pathways or protein degradation. These various forms of intracellular antibodies have largely been used as research tools to investigate function within cells by perturbing protein activity. New applications of such molecules are on the horizon, namely their use as drugs per se and as templates for small-molecule drug discovery. The former is a potential new pharmacology that could harness the power and flexibility of molecular biology to generate new classes of drugs (herein referred to as macrodrugs when used in the context of disease control). Delivery of engineered intracellular antibodies, and other antigen-binding macromolecules formats, into cells to produce a therapeutic effect could be applied to any therapeutic area where regulation, degradation or other kinds of manipulation of target proteins can produce a therapeutic effect. Further, employing single-domain antibody fragments as competitors in small-molecule screening has been shown to enable identification of drug hits from diverse chemical libraries. Compounds selected in this way can mimic the effects of the intracellular antibodies that have been used for target validation. The capability of intracellular antibodies to discriminate between closely related proteins lends a new dimension to drug screening and drug development. Full article
(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)
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25 pages, 5519 KiB  
Article
Defensin Interactions in Relation to Monoclonal and Disease-Related Proteinase 3 Antibodies Binding at the Catalytic Site
by Morten Zoega, Nicole Hartwig Trier, Rikke Guldhammer Nejrup, Anna Chailyan, Tina Friis, Peter Højrup and Gunnar Houen
Antibodies 2023, 12(1), 23; https://doi.org/10.3390/antib12010023 - 13 Mar 2023
Viewed by 2088
Abstract
Proteinase 3 (PR3) is a neutrophil granulocyte enzyme and an autoantigen found in several forms of vasculitis. Due to the diagnostic and clinical importance of antibodies (Abs) to PR3, it is important to characterize the protein and the nature of its epitopes. Here, [...] Read more.
Proteinase 3 (PR3) is a neutrophil granulocyte enzyme and an autoantigen found in several forms of vasculitis. Due to the diagnostic and clinical importance of antibodies (Abs) to PR3, it is important to characterize the protein and the nature of its epitopes. Here, we have characterized PR3 monoclonal antibodies (MAbs) and disease-associated Abs and their dependency on the PR3 structure and modifications, especially interactions with α-defensins. Three MAbs (HYB 172-01, 172-04, 172-05), which bind to PR3 in its native and denatured forms and provide the disulphide bridges, were intact. α-1-antitrypsin (AT) binds to purified human neutrophil granulocyte PR3 and inhibits its proteolytic activity, towards a small synthetic peptide substrate and a large protein substrate (casein). AT also inhibited the binding of the three MAbs to PR3, indicating that they bind in a region affected by AT binding. However, the MAbs did not inhibit PR3 proteolytic activity with a small substrate, showing that they bound at the active site without restricting access to the substrate cleft. Patient-derived Abs showed essentially the same characteristics as the MAbs, with important implications for vasculitis diagnostics and pathophysiology. Current findings illustrate that PR3 epitopes depend on the three-dimensional structure of the PR3/defensin complex, and that the epitopes depend to a smaller or larger degree on PR3/defensin associations. Full article
(This article belongs to the Special Issue Antibodies: 10th Anniversary)
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9 pages, 490 KiB  
Article
Safety, Tolerability, and Immunogenicity of V160, a Conditionally Replication-Defective Cytomegalovirus Vaccine, in Healthy Japanese Men in a Randomized, Controlled Phase 1 Study
by Shinya Murata, Nobuyuki Oshima, Takashi Iwasa, Yukako Fukao and Miyuki Sawata
Antibodies 2023, 12(1), 22; https://doi.org/10.3390/antib12010022 - 10 Mar 2023
Cited by 1 | Viewed by 1996
Abstract
Cytomegalovirus (CMV) infection can cause newborn morbidity and mortality; no pharmacological method of reducing CMV infection during pregnancy is currently available. In a phase 1 study in the United States, V160, a conditionally replication-defective CMV vaccine, was immunogenic and well tolerated. This placebo-controlled [...] Read more.
Cytomegalovirus (CMV) infection can cause newborn morbidity and mortality; no pharmacological method of reducing CMV infection during pregnancy is currently available. In a phase 1 study in the United States, V160, a conditionally replication-defective CMV vaccine, was immunogenic and well tolerated. This placebo-controlled study (NCT03840174) investigated the safety and immunogenicity of a three-dose V160 vaccine administered over six months. A total of 18 healthy adult Japanese males (9 seronegative and 9 seropositive) were enrolled at a single center and randomized 2:1 to intramuscular V160 or placebo. In vitro, V160 induced high CMV-specific neutralizing antibody (NAb) titers (50% neutralization titer [NT50], 3651; 95% confidence interval [CI], 1688–7895) in the CMV-seronegative per-protocol immunogenicity (PPI) population one month after the third vaccine dose was administered compared with no change in the placebo arm (NT50, <94; 95% CI <94–115). The geometric mean titer ratio in the seronegative population versus baseline was 77.7 (95% CI, 23.9–252.4). CMV NAb titers in the CMV-seropositive PPI population were similar to baseline NAb titers observed in the CMV-seropositive population. V160 was well tolerated, and no vaccine viral DNA shedding was observed. In conclusion, the immunogenicity and safety profile of V160 in Japanese participants was consistent with other populations. Full article
(This article belongs to the Section Humoral Immunity)
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16 pages, 606 KiB  
Review
Cutaneous Lymphoma and Antibody-Directed Therapies
by Alvise Sernicola, Christian Ciolfi, Paola Miceli and Mauro Alaibac
Antibodies 2023, 12(1), 21; https://doi.org/10.3390/antib12010021 - 3 Mar 2023
Cited by 1 | Viewed by 2684
Abstract
The introduction of monoclonal antibodies such as rituximab to the treatment of cancer has greatly advanced the treatment scenario in onco-hematology. However, the response to these agents may be limited by insufficient efficacy or resistance. Antibody–drug conjugates are an attractive strategy to deliver [...] Read more.
The introduction of monoclonal antibodies such as rituximab to the treatment of cancer has greatly advanced the treatment scenario in onco-hematology. However, the response to these agents may be limited by insufficient efficacy or resistance. Antibody–drug conjugates are an attractive strategy to deliver payloads of toxicity or radiation with high selectivity toward malignant targets and limited unwanted effects. Primary cutaneous lymphomas are a heterogeneous group of disorders and a current area of unmet need in dermato-oncology due to the limited options available for advanced cases. This review briefly summarizes our current understanding of T and B cell lymphomagenesis, with a focus on recognized molecular alterations that may provide investigative therapeutic targets. The authors reviewed antibody-directed therapies investigated in the setting of lymphoma: this term includes a broad spectrum of approaches, from antibody–drug conjugates such as brentuximab vedotin, to bi-specific antibodies, antibody combinations, antibody-conjugated nanotherapeutics, radioimmunotherapy and, finally, photoimmunotherapy with specific antibody–photoadsorber conjugates, as an attractive strategy in development for the future management of cutaneous lymphoma. Full article
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24 pages, 1399 KiB  
Review
Intravenous Immunoglobulins as Immunomodulators in Autoimmune Diseases and Reproductive Medicine
by Tsvetelina Velikova, Metodija Sekulovski, Simona Bogdanova, Georgi Vasilev, Monika Peshevska-Sekulovska, Dimitrina Miteva and Tsvetoslav Georgiev
Antibodies 2023, 12(1), 20; https://doi.org/10.3390/antib12010020 - 2 Mar 2023
Cited by 8 | Viewed by 4855
Abstract
Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few [...] Read more.
Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes. Full article
(This article belongs to the Special Issue Antibodies: 10th Anniversary)
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13 pages, 2198 KiB  
Article
Pilot Study Results on Antibodies to the S- and N-Proteins of SARS-CoV-2 in Paired Sera from COVID-19 Patients with Varying Severity
by Yulia Desheva, Anna Lerner, Tamara Shvedova, Olga Kopteva, Polina Kudar, Irina Koroleva, Galina Leontieva and Alexander Suvorov
Antibodies 2023, 12(1), 19; https://doi.org/10.3390/antib12010019 - 27 Feb 2023
Cited by 1 | Viewed by 2244
Abstract
In this retrospective cohort study, we investigated the formation of individual classes of antibodies to SARS-CoV-2 in archived serial sera from hospitalized patients with the medium–severe (n = 17) and severe COVID-19 (n = 11). The serum/plasma samples were studied for [...] Read more.
In this retrospective cohort study, we investigated the formation of individual classes of antibodies to SARS-CoV-2 in archived serial sera from hospitalized patients with the medium–severe (n = 17) and severe COVID-19 (n = 11). The serum/plasma samples were studied for the presence of IgG, IgM and IgA antibodies to the recombinant S- and N-proteins of SARS-CoV-2. By the 7th day of hospitalization, an IgG increase was observed in patients both with a positive PCR test and without PCR confirmation of SARS-CoV-2 infection. Significant increases in the anti-spike IgG levels were noted only in moderate COVID-19. The four-fold increase of IgM to N-protein was obtained more often in the groups with mild and moderate infections. The IgA levels decreased during the infection to both the S- and N-proteins, and the most pronounced decrease was in the severe COVID-19 patients. The serum IgG to S-protein one week after hospitalization demonstrated a high-power relationship (rs = 0.75) with the level of RBD antibodies. There was a medium strength relationship between the levels of CRP and IgG (rs = 0.43). Thus, in patients with acute COVID-19, an increase in antibodies can develop as early as 1 week of hospital stay. The SARS-CoV-2 antibody conversions may confirm SARS-CoV-2 infection in PCR-negative patients. Full article
(This article belongs to the Special Issue The Role of Antibodies in SARS-CoV-2 Infection)
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14 pages, 1769 KiB  
Review
Serological Cross-Reactivity in Zoonotic Flaviviral Infections of Medical Importance
by Priscilla Gomes da Silva, José Augusto Seixas dos Reis, Marcio Nogueira Rodrigues, Quézia da Silva Ardaya and João Rodrigo Mesquita
Antibodies 2023, 12(1), 18; https://doi.org/10.3390/antib12010018 - 24 Feb 2023
Cited by 5 | Viewed by 2872
Abstract
Flaviviruses are enveloped RNA viruses from the family Flaviviridae that comprise many important human pathogenic arboviruses such as Yellow Fever, Dengue, and Zika viruses. Because they belong to the same genus, these viruses show sequence and structural homology among them, which results in [...] Read more.
Flaviviruses are enveloped RNA viruses from the family Flaviviridae that comprise many important human pathogenic arboviruses such as Yellow Fever, Dengue, and Zika viruses. Because they belong to the same genus, these viruses show sequence and structural homology among them, which results in serological cross-reactivity. Upon infection, the immune system produces both species-specific and cross-reactive antibodies, and depending on the virus, in a successive flavivirus infection, cross-reactive antibodies either enhance protection or exacerbate the disease—the latter usually due to antibody-dependent enhancement. These antigenic relationships between different flaviviruses that lead to serological cross-reactivity make them difficult to be identified through serological methods, especially when it comes to successive flavivirus infections. We present here an overview of the main structural, epidemiological, and immunological aspects of flaviviruses, highlighting the role of neutralizing antibodies in fighting viral infections and in the “original antigenic sin” problem. Finally, we draw attention to the importance of developing a rapid serological diagnostic test for flaviviruses with high sensitivity and specificity, especially when considering that cross-reactive immunity can influence the outcome of these infections. Full article
(This article belongs to the Section Humoral Immunity)
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21 pages, 5493 KiB  
Article
Comparative Binding Ability of Human Monoclonal Antibodies against Omicron Variants of SARS-CoV-2: An In Silico Investigation
by Nabarun Chandra Das, Pritha Chakraborty, Jagadeesh Bayry and Suprabhat Mukherjee
Antibodies 2023, 12(1), 17; https://doi.org/10.3390/antib12010017 - 23 Feb 2023
Cited by 10 | Viewed by 3026
Abstract
Mutation(s) in the spike protein is the major characteristic trait of newly emerged SARS-CoV-2 variants such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Delta-plus. Omicron (B.1.1.529) is the latest addition and it has been characterized by high transmissibility and the [...] Read more.
Mutation(s) in the spike protein is the major characteristic trait of newly emerged SARS-CoV-2 variants such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Delta-plus. Omicron (B.1.1.529) is the latest addition and it has been characterized by high transmissibility and the ability to escape host immunity. Recently developed vaccines and repurposed drugs exert limited action on Omicron strains and hence new therapeutics are immediately needed. Herein, we have explored the efficiency of twelve therapeutic monoclonal antibodies (mAbs) targeting the RBD region of the spike glycoprotein against all the Omicron variants bearing a mutation in spike protein through molecular docking and molecular dynamics simulation. Our in silico evidence reveals that adintivimab, beludivimab, and regadanivimab are the most potent mAbs to form strong biophysical interactions and neutralize most of the Omicron variants. Considering the efficacy of mAbs, we incorporated CDRH3 of beludavimab within the framework of adintrevimab, which displayed a more intense binding affinity towards all of the Omicron variants viz. BA.1, BA.2, BA.2.12.1, BA.4, and BA.5. Furthermore, the cDNA of chimeric mAb was cloned in silico within pET30ax for recombinant production. In conclusion, the present study represents the candidature of human mAbs (beludavimab and adintrevimab) and the therapeutic potential of designed chimeric mAb for treating Omicron-infected patients. Full article
(This article belongs to the Special Issue Coronavirus-Targeting Antibodies)
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Graphical abstract

8 pages, 1358 KiB  
Communication
Bioprocess Development and Characterization of a 13C-Labeled Hybrid Bispecific Antibody Produced in Escherichia coli
by Aaron T. Wecksler, Victor Lundin, Ambrose J. Williams, Karthik Veeravalli, Dorothea E. Reilly and Sung-Hye Grieco
Antibodies 2023, 12(1), 16; https://doi.org/10.3390/antib12010016 - 14 Feb 2023
Cited by 2 | Viewed by 1904
Abstract
Monoclonal antibodies (mAbs) are highly efficacious therapeutics; however, due to their large, dynamic nature, structural perturbations and regional modifications are often difficult to study. Moreover, the homodimeric, symmetrical nature of mAbs makes it difficult to elucidate which heavy chain (HC)-light chain (LC) pairs [...] Read more.
Monoclonal antibodies (mAbs) are highly efficacious therapeutics; however, due to their large, dynamic nature, structural perturbations and regional modifications are often difficult to study. Moreover, the homodimeric, symmetrical nature of mAbs makes it difficult to elucidate which heavy chain (HC)-light chain (LC) pairs are responsible for any structural changes, stability concerns, and/or site-specific modifications. Isotopic labeling is an attractive means for selectively incorporating atoms with known mass differences to enable identification/monitoring using techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR). However, the isotopic incorporation of atoms into proteins is typically incomplete. Here we present a strategy for incorporating 13C-labeling of half antibodies using an Escherichia coli fermentation system. Unlike previous attempts to generate isotopically labeled mAbs, we provide an industry-relevant, high cell density process that yielded >99% 13C-incorporation using 13C-glucose and 13C-celtone. The isotopic incorporation was performed on a half antibody designed with knob-into-hole technology to enable assembly with its native (naturally abundant) counterpart to generate a hybrid bispecific (BsAb) molecule. This work is intended to provide a framework for producing full-length antibodies, of which half are isotopically labeled, in order to study the individual HC-LC pairs. Full article
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19 pages, 6552 KiB  
Review
Non-Affinity Purification of Antibodies
by Tsutomu Arakawa, Yui Tomioka, Masataka Nakagawa, Chiaki Sakuma, Yasunori Kurosawa, Daisuke Ejima, Kouhei Tsumoto and Teruo Akuta
Antibodies 2023, 12(1), 15; https://doi.org/10.3390/antib12010015 - 13 Feb 2023
Cited by 5 | Viewed by 4986
Abstract
Currently, purification of antibodies is mainly carried out using a platform technology composed primarily of Protein A chromatography as a capture step, regardless of the scale. However, Protein A chromatography has a number of drawbacks, which are summarized in this review. As an [...] Read more.
Currently, purification of antibodies is mainly carried out using a platform technology composed primarily of Protein A chromatography as a capture step, regardless of the scale. However, Protein A chromatography has a number of drawbacks, which are summarized in this review. As an alternative, we propose a simple small-scale purification protocol without Protein A that uses novel agarose native gel electrophoresis and protein extraction. For large-scale antibody purification, we suggest mixed-mode chromatography that can in part mimic the properties of Protein A resin, focusing on 4-Mercapto-ethyl-pyridine (MEP) column chromatography. Full article
(This article belongs to the Special Issue Antibodies: 10th Anniversary)
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20 pages, 4761 KiB  
Article
Characterization of an IDH1 R132H Rabbit Monoclonal Antibody, MRQ-67, and Its Applications in the Identification of Diffuse Gliomas
by Raul Copaciu, Juliet Rashidian, Joshua Lloyd, Aril Yahyabeik, Jennifer McClure, Kelsea Cummings and Qin Su
Antibodies 2023, 12(1), 14; https://doi.org/10.3390/antib12010014 - 6 Feb 2023
Viewed by 2779
Abstract
The current diagnosis of diffuse glioma involves isocitrate dehydrogenase (IDH) mutation testing. Most IDH mutant gliomas carry a G-to-A mutation at IDH1 position 395, resulting in the R132H mutant. R132H immunohistochemistry (IHC), therefore, is used to screen for the IDH1 mutation. [...] Read more.
The current diagnosis of diffuse glioma involves isocitrate dehydrogenase (IDH) mutation testing. Most IDH mutant gliomas carry a G-to-A mutation at IDH1 position 395, resulting in the R132H mutant. R132H immunohistochemistry (IHC), therefore, is used to screen for the IDH1 mutation. In this study, the performance of MRQ-67, a recently generated IDH1 R132H antibody, was characterized in comparison with H09, a frequently used clone. Selective binding was demonstrated by an enzyme-linked immunosorbent assay for MRQ-67 to the R132H mutant, with an affinity higher than that for H09. By Western and dot immunoassays, MRQ-67 was found to bind specifically to the IDH1 R1322H, with a higher capacity than H09. IHC testing with MRQ-67 demonstrated a positive signal in most diffuse astrocytomas (16/22), oligodendrogliomas (9/15), and secondary glioblastomas tested (3/3), but not in primary glioblastomas (0/24). While both clones demonstrated a positive signal with similar patterns and equivalent intensities, H09 exhibited a background stain more frequently. DNA sequencing on 18 samples showed the R132H mutation in all IHC positive cases (5/5), but not in negative cases (0/13). These results demonstrate that MRQ-67 is a high-affinity antibody suitable for specific detection of the IDH1 R132H mutant by IHC and with less background as compared with H09. Full article
(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy Series II)
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9 pages, 1418 KiB  
Case Report
Anti-RuvBL1/2 Autoantibodies Detection in a Patient with Overlap Systemic Sclerosis and Polymyositis
by Linda Di Pietro, Fabio Chiccoli, Lorenzo Salvati, Emanuele Vivarelli, Alessandra Vultaggio, Andrea Matucci, Chelsea Bentow, Michael Mahler, Paola Parronchi and Boaz Palterer
Antibodies 2023, 12(1), 13; https://doi.org/10.3390/antib12010013 - 3 Feb 2023
Cited by 2 | Viewed by 2231
Abstract
Anti-RuvBL1/2 autoantibodies have recently been detected in patients with systemic sclerosis (SSc) and scleromyositis overlap syndromes. These autoantibodies exhibit a distinct speckled pattern in an indirect immunofluorescent assay on Hep-2 cells. We report the case of a 48 year old man with facial [...] Read more.
Anti-RuvBL1/2 autoantibodies have recently been detected in patients with systemic sclerosis (SSc) and scleromyositis overlap syndromes. These autoantibodies exhibit a distinct speckled pattern in an indirect immunofluorescent assay on Hep-2 cells. We report the case of a 48 year old man with facial changes, Raynaud’s phenomenon, puffy fingers, and muscle pain. A speckled pattern on Hep-2 cells was identified, but the conventional antibody testing was negative. Based on the clinical suspicion and the ANA pattern, further testing was sought demonstrating anti-RuvBL1/2 autoantibodies. Hence, a review of the English literature was performed to define this newly emerging clinical–serological syndrome. With the one here reported, a total of 52 cases have been described to date (December 2022). Anti-RuvBL1/2 autoantibodies are highly specific for SSc and are associated with SSc/PM overlaps. Apart from myopathy, gastrointestinal and pulmonary involvement are frequently observed in these patients (94% and 88%, respectively). Full article
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4 pages, 191 KiB  
Editorial
Antibodies, B Cell Responses and Immune Responses to SARS-CoV-2 Infections
by Luis Martinez-Sobrido and James J. Kobie
Antibodies 2023, 12(1), 12; https://doi.org/10.3390/antib12010012 - 1 Feb 2023
Viewed by 1620
Abstract
Coronaviruses (CoV) are enveloped, positive-sense, single-stranded RNA viruses responsible for causing seasonal, mild respiratory disease in humans [...] Full article
9 pages, 960 KiB  
Communication
Determination of the Binding Epitope of an Anti-Mouse CCR9 Monoclonal Antibody (C9Mab-24) Using the 1× Alanine and 2× Alanine-Substitution Method
by Hiyori Kobayashi, Teizo Asano, Tomohiro Tanaka, Hiroyuki Suzuki, Mika K. Kaneko and Yukinari Kato
Antibodies 2023, 12(1), 11; https://doi.org/10.3390/antib12010011 - 31 Jan 2023
Cited by 1 | Viewed by 2265
Abstract
C-C chemokine receptor 9 (CCR9) is a receptor for C-C-chemokine ligand 25 (CCL25). CCR9 is crucial in the chemotaxis of immune cells and inflammatory responses. Moreover, CCR9 is highly expressed in tumors, including several solid tumors and T-cell acute lymphoblastic leukemia. Several preclinical [...] Read more.
C-C chemokine receptor 9 (CCR9) is a receptor for C-C-chemokine ligand 25 (CCL25). CCR9 is crucial in the chemotaxis of immune cells and inflammatory responses. Moreover, CCR9 is highly expressed in tumors, including several solid tumors and T-cell acute lymphoblastic leukemia. Several preclinical studies have shown that anti-CCR9 monoclonal antibodies (mAbs) exert antitumor activity. Therefore, CCR9 is an attractive target for tumor therapy. In this study, we conducted the epitope mapping of an anti-mouse CCR9 (mCCR9) mAb, C9Mab-24 (rat IgG2a, kappa), using the 1× alanine (1× Ala)- and 2× alanine (2× Ala)-substitution methods via enzyme-linked immunosorbent assay. We first performed the 1× Ala-substitution method using one alanine-substituted peptides of the mCCR9 N-terminus (amino acids 1–19). C9Mab-24 did not recognize two peptides (F14A and F17A), indicating that Phe14 and Phe17 are critical for C9Mab-24-binding to mCCR9. Furthermore, we conducted the 2× Ala-substitution method using two consecutive alanine-substituted peptides of the mCCR9 N-terminus, and showed that C9Mab-24 did not react with four peptides (M13A–F14A, F14A–D15A, D16A–F17A, and F17A–S18A), indicating that 13-MFDDFS-18 is involved in C9Mab-24-binding to mCCR9. Overall, combining, the 1× Ala- or 2× Ala-scanning methods could be useful for understanding for target–antibody interaction. Full article
(This article belongs to the Special Issue Antibodies: 10th Anniversary)
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7 pages, 1535 KiB  
Case Report
Rapidly Progressive Pauci-Immune Glomerulonephritis with Aberrant Fibrinoid Necrosis Associated with Atezolizumab, an Immune Check Point Inhibitor: A Case Report and Review of Literature
by Petros Nikolopoulos, George Liapis, Panagiotis Giannakopoulos, Ioannis Kotsantis, Konstantinos Drouzas and Sophia Lionaki
Antibodies 2023, 12(1), 10; https://doi.org/10.3390/antib12010010 - 25 Jan 2023
Cited by 3 | Viewed by 1954
Abstract
Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity [...] Read more.
Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity of ICIs is limited. Herein, we present a patient with lung cancer treated with atezolizumab, an IgG1 monoclonal antibody aimed at the programmed death ligand 1 (PD-L1), who presented with vasculitic skin rash and rapidly deteriorating renal function, new onset of significant glomerular hematuria and proteinuria. The renal biopsy revealed acute necrotizing pauci-immune vasculitis, with fibrinoid necrosis. The patient received a course of high-dose glucocorticoids with recovery of renal function and skin lesions. Further immunosuppressive therapy was withheld, due to active malignancy in the lung, while oncology consultation recommended the continuation of treatment with atezolizumab, as the patient had shown substantial response. Full article
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13 pages, 6949 KiB  
Article
Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody
by Maile Velasquez, Chris O’Sullivan, Robert Brockett, Amanda Mikels-Vigdal, Igor Mikaelian, Victoria Smith and Andrew E. Greenstein
Antibodies 2023, 12(1), 9; https://doi.org/10.3390/antib12010009 - 18 Jan 2023
Cited by 2 | Viewed by 2912
Abstract
Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated [...] Read more.
Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. Together, our findings provide insights into the distribution and potential role of MMP9 in inflammatory diseases. Full article
(This article belongs to the Special Issue Antibodies: 10th Anniversary)
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3 pages, 188 KiB  
Editorial
Acknowledgment to the Reviewers of Antibodies in 2022
by Antibodies Editorial Office
Antibodies 2023, 12(1), 8; https://doi.org/10.3390/antib12010008 - 17 Jan 2023
Viewed by 1296
Abstract
High-quality academic publishing is built on rigorous peer review [...] Full article
6 pages, 543 KiB  
Commentary
Therapeutic Phage Display-Derived Single-Domain Antibodies for Pandemic Preparedness
by Janet M. Daly, Theam Soon Lim and Kevin C. Gough
Antibodies 2023, 12(1), 7; https://doi.org/10.3390/antib12010007 - 14 Jan 2023
Cited by 3 | Viewed by 2926
Abstract
Driven by necessity, the COVID-19 pandemic caused by SARS-CoV-2 has accelerated the development and implementation of new vaccine platforms and other viral therapeutics. Among these is the therapeutic use of antibodies including single-domain antibodies, in particular the camelid variable heavy-chain fragment (VHH). Such [...] Read more.
Driven by necessity, the COVID-19 pandemic caused by SARS-CoV-2 has accelerated the development and implementation of new vaccine platforms and other viral therapeutics. Among these is the therapeutic use of antibodies including single-domain antibodies, in particular the camelid variable heavy-chain fragment (VHH). Such therapies can provide a critical interim intervention when vaccines have not yet been developed for an emerging virus. It is evident that an increasing number of different viruses are emerging and causing epidemics and pandemics with increasing frequency. It is therefore imperative that we capitalize on the experience and knowledge gained from combatting COVID-19 to be better prepared for the next pandemic. Full article
(This article belongs to the Special Issue Coronavirus-Targeting Antibodies)
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4 pages, 210 KiB  
Editorial
Design, Production, Characterization, and Use of Peptide Antibodies
by Nicole H. Trier and Gunnar Houen
Antibodies 2023, 12(1), 6; https://doi.org/10.3390/antib12010006 - 13 Jan 2023
Viewed by 2515
Abstract
Antibodies are key reagents in diagnostics, therapeutics, and experimental biology, capable of detecting numerous targets [...] Full article
(This article belongs to the Special Issue Design, Production and Characterization of Peptide Antibodies)
16 pages, 1299 KiB  
Review
A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19)
by Kristin Widyasari and Jinnam Kim
Antibodies 2023, 12(1), 5; https://doi.org/10.3390/antib12010005 - 11 Jan 2023
Cited by 15 | Viewed by 3877
Abstract
Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies’ efficacy and long-term viability. Studies reported several antibodies, that received authorization for COVID-19 treatment, are not effective against new variants or subvariants of SARS-CoV-2, [...] Read more.
Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies’ efficacy and long-term viability. Studies reported several antibodies, that received authorization for COVID-19 treatment, are not effective against new variants or subvariants of SARS-CoV-2, hence their distribution has to be paused. Here, the authors reviewed the status of the currently available monoclonal antibodies for COVID-19 treatment, their potential as a therapeutic agent, and the challenges ahead. To address these issues, the authors presented general information on SARS-CoV-2 and how monoclonal antibodies work against SARS-CoV-2. The authors then focus on the antibodies that have been deployed for COVID-19 treatment and their current status, as well as the evidence supporting their potential as an early intervention against COVID-19. Lastly, the authors discussed some leading obstacles that hinder the development and administration of monoclonal antibodies for the treatment of COVID-19. Full article
(This article belongs to the Special Issue The Role of Antibodies in SARS-CoV-2 Infection)
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11 pages, 893 KiB  
Review
TLR7 and IgM: Dangerous Partners in Autoimmunity
by Timm Amendt and Philipp Yu
Antibodies 2023, 12(1), 4; https://doi.org/10.3390/antib12010004 - 6 Jan 2023
Cited by 2 | Viewed by 3729
Abstract
The B cell antigen receptor (BCR)-repertoire is capable of recognizing a nearly unlimited number of antigens. Inevitably, the random nature of antibody gene segment rearrangement, needed in order to provide mature B cells, will generate autoreactive specificities. Once tolerance mechanisms fail to block [...] Read more.
The B cell antigen receptor (BCR)-repertoire is capable of recognizing a nearly unlimited number of antigens. Inevitably, the random nature of antibody gene segment rearrangement, needed in order to provide mature B cells, will generate autoreactive specificities. Once tolerance mechanisms fail to block the activation and differentiation of autoreactive B cells, harmful autoantibodies may get secreted establishing autoimmune diseases. Besides the hallmark of autoimmunity, namely IgG autoantibodies, IgM autoantibodies are also found in many autoimmune diseases. In addition to pathogenic functions of secreted IgM the IgM-BCR expressing B cell might be the initial check-point where, in conjunction with innate receptor signals, B cell mediated autoimmunity starts it fateful course. Recently, pentameric IgM autoantibodies have been shown to contribute significantly to the pathogenesis of various autoimmune diseases, such as rheumatoid arthritis (RA), autoimmune hemolytic anemia (AIHA), pemphigus or autoimmune neuropathy. Further, recent studies suggest differences in the recognition of autoantigen by IgG and IgM autoantibodies, or propose a central role of anti-ACE2-IgM autoantibodies in severe COVID-19. However, exact mechanisms still remain to be uncovered in detail. This article focuses on summarizing recent findings regarding the importance of autoreactive IgM in establishing autoimmune diseases. Full article
(This article belongs to the Section Humoral Immunity)
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13 pages, 1115 KiB  
Review
Specific Autoantibodies and Microvascular Damage Progression Assessed by Nailfold Videocapillaroscopy in Systemic Sclerosis: Are There Peculiar Associations? An Update
by Elvis Hysa, Rosanna Campitiello, Silvia Sammorì, Emanuele Gotelli, Andrea Cere, Giampaola Pesce, Carmen Pizzorni, Sabrina Paolino, Alberto Sulli, Vanessa Smith and Maurizio Cutolo
Antibodies 2023, 12(1), 3; https://doi.org/10.3390/antib12010003 - 4 Jan 2023
Cited by 3 | Viewed by 2561
Abstract
Background: Specific autoantibodies and nailfold videocapillaroscopy (NVC) findings are serum and morphological diagnostic hallmarks of systemic sclerosis (SSc) as well as useful biomarkers which stratify the microvascular progression and prognosis of patients. Methods: The aim of our narrative review is to provide an [...] Read more.
Background: Specific autoantibodies and nailfold videocapillaroscopy (NVC) findings are serum and morphological diagnostic hallmarks of systemic sclerosis (SSc) as well as useful biomarkers which stratify the microvascular progression and prognosis of patients. Methods: The aim of our narrative review is to provide an update and overview of the link between SSc-related autoantibodies, used in clinical practice, and microvascular damage, evaluated by NVC, by exploring the interaction between these players in published studies. A narrative review was conducted by searching relevant keywords related to this field in Pubmed, Medline and EULAR/ACR conference abstracts with a focus on the findings published in the last 5 years. Results: Our search yielded 13 clinical studies and 10 pre-clinical studies. Most of the clinical studies (8/13, 61.5%) reported a significant association between SSc-related autoantibodies and NVC patterns: more specifically anti-centromere autoantibodies (ACA) were associated more often with an “Early” NVC pattern, whereas anti-topoisomerase autoantibodies (ATA) more frequently showed an “Active” or “Late” NVC pattern. Five studies, instead, did not find a significant association between specific autoantibodies and NVC findings. Among the pre-clinical studies, SSc-related autoantibodies showed different mechanisms of damage towards both endothelial cells, fibroblasts and smooth muscle vascular cells. Conclusions: The clinical and laboratory evidence on SSc-related autoantibodies and microvascular damage shows that these players are interconnected. Further clinical and demographic factors (e.g., age, sex, disease duration, treatment and comorbidities) might play an additional role in the SSc-related microvascular injury whose progression appears to be complex and multifactorial. Full article
(This article belongs to the Special Issue New, Old, and Shared Antibody Specificities in Autoimmune Diseases)
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11 pages, 1199 KiB  
Article
The Seroprevalence and Seropositivity of SARS-CoV-2 among Healthcare Workers during the Third Pandemic Wave
by Atefeh Vaezi, Hamed Fakhim, Saeed Abbasi, Soraya Masoudi, Mahnaz Hosseini Rizi and Shaghayegh Haghjooy Javanmard
Antibodies 2023, 12(1), 2; https://doi.org/10.3390/antib12010002 - 23 Dec 2022
Cited by 1 | Viewed by 2005
Abstract
Background: Due to the unclear protective role of produced antibodies and the need for seroepidemiologic studies, we surveyed the COVID-19 seroprevalence among healthcare professionals who had direct or indirect contact with COVID-19 patients. Methods: From 19 October 2020 to 17 February 2021, 300 [...] Read more.
Background: Due to the unclear protective role of produced antibodies and the need for seroepidemiologic studies, we surveyed the COVID-19 seroprevalence among healthcare professionals who had direct or indirect contact with COVID-19 patients. Methods: From 19 October 2020 to 17 February 2021, 300 healthcare workers were enrolled and tested for serum antibodies in this prospective cohort study. Demographic information, risk factors, and infection history were collected. Anti- SARS-CoV-2 IgG and IgM antibody titers were determined to estimate the seroconversion rate. Results: During the first and second phases of the study, the positive seroconversion rates were 31.7 and 26.6%, respectively. In seronegative individuals, sixteen (10.6%) new cases of COVID-19 and five (6.3%) reinfections were identified. Among those with a positive antibody level, forty-one (36.9%) healthcare workers reported no symptoms in the preceding months. There was no association between occupational exposure and an increased probability of seroconversion. Conclusions: The seropositivity rate and the rate of asymptomatic individuals with seroconversion was remarkable and could be an indicator of a high infection rate among healthcare workers. Full article
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9 pages, 565 KiB  
Opinion
Philosophical Approach to Neural Autoantibodies in Psychiatric Disease—Multi-Systemic Dynamic Continuum from Protective to Harmful Autoimmunity in Neuronal Systems
by Niels Hansen
Antibodies 2023, 12(1), 1; https://doi.org/10.3390/antib12010001 - 23 Dec 2022
Viewed by 1807
Abstract
(1) Background: philosophical views are important to enable a general and multi-systemic view of the potential understanding of autoimmunity in psychiatric disease that is not solely reflected by an immunological viewpoint. (2) Methods: we reviewed current theories of autoimmunity. (3) Results: we propose [...] Read more.
(1) Background: philosophical views are important to enable a general and multi-systemic view of the potential understanding of autoimmunity in psychiatric disease that is not solely reflected by an immunological viewpoint. (2) Methods: we reviewed current theories of autoimmunity. (3) Results: we propose a novel area view integrating the “self/non-self” and “continuity” model into the expression of varied forms of autoimmunity in psychiatric disease, ranging from protective to harmful autoimmunity consequences framed into micro-systems (nerve cells) and macro-systems (neuronal networks), termed the “multi-systemic dynamic continuum model”. (4) Conclusions: autoimmunity’s dynamic spectrum is delineated here as something that probably functions as a whole entity to maintain, first of all, human homeostasis in behavior affecting cells or neuronal networks differently, and secondly to prevent psychiatric disease. Full article
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