Autoimmune and Inflammatory Rheumatic Diseases: Potential Biomarkers, Antibodies Response and New Therapies

A special issue of Antibodies (ISSN 2073-4468). This special issue belongs to the section "Antibody-Based Diagnostics".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 25780

Special Issue Editor


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Guest Editor
Division of Clinical Immunology, Department of Clinical, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
Interests: inflammatory rheumatic diseases; autoimmunity; T-cell response
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Special Issue Information

Dear Colleagues,

Autoimmune and inflammatory rheumatic diseases encompass a broad spectrum of conditions with severe disabling effects and potential organ damage. They mainly include systemic lupus erythematosus (SLE), vasculitis, rheumatoid arthritis, and spondylarthritis. Antibodies play a very important role in these diseases. In fact, several are important for pathogenesis, as exemplified by anti-native DNA antibodies associated with kidney damage in SLE, anti-neutrophil cytoplasmic antibodies (ANCAs) playing a key role in the pathogenesis of small-vessel vasculitis, and anti-citrullinated cyclic peptide (CCP) antibodies associated with an erosive course of rheumatoid arthritis. Anti-nuclear antibodies (ANAs), ANCAs, and anti-CCP antibodies also have a fundamental role in the diagnosis of these diseases. From a therapeutic point of view, monoclonal antibodies such as anti-B-cell, anti-cytokine, and anti-interleukin biologics have been used for the treatment of these conditions for the last 20 years, significantly changing the quality of life and prognosis of patients. However, important unmet needs still remain, such as the unavailability of biomarkers for diagnosis and prediction of the response to various biologics as well as the availability of more effective antibodies that may be used to target newly discovered pro-inflammatory molecules.

We invite contributions from experienced scientists and clinicians to this Special Issue of Antibodies, which hopes to further advance knowledge in this field to reduce the suffering and disability of patients with autoimmune and inflammatory rheumatic diseases.

Dr. Marino Paroli
Guest Editor

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Keywords

  • antibodies and arthritis
  • antibodies and connective tissue diseases
  • anti-phospholipid syndrome
  • anti-COVID-19 response in rheumatic diseases
  • biomarkers in autoimmune/rheumatic diseases
  • biologics

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Published Papers (6 papers)

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Research

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22 pages, 1874 KiB  
Article
Antibodies for β2-Microglobulin and the Heavy Chains of HLA-E, HLA-F, and HLA-G Reflect the HLA-Variants on Activated Immune Cells and Phases of Disease Progression in Rheumatoid Arthritis Patients under Treatment
by Mepur H. Ravindranath, Narendranath M. Ravindranath, Carly J. Amato-Menker, Fatiha El Hilali, Senthamil R. Selvan, Edward J. Filippone and Luis Eduardo Morales-Buenrostro
Antibodies 2023, 12(2), 26; https://doi.org/10.3390/antib12020026 - 31 Mar 2023
Viewed by 2661
Abstract
Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against “altered” autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, [...] Read more.
Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against “altered” autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo “alteration” during activation of immune cells, resulting in β2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). β2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs against both β2m and HCs of HLA-E, HLA-F, and HLA-G in 74 RA patients receiving immunosuppressive drugs. Anti-β2m IgM was present in 20 of 74 patients, whereas anti-β2m IgG was found in only 8 patients. Abs against β2m would be expected if Abs were generated against β2m-associated HLA HCs. The majority of patients were devoid of either anti-β2m IgM or IgG but had Abs against HCs of different HLA-Ib molecules. The paucity of anti-β2m Abs in this cohort of patients suggests that Abs were developed against β2m-free HLA HCs, such as Face-2, Face-3, and Face-4. While 63 of 68 patients had IgG Abs against anti-HLA-F HCs, 36 and 50 patients showed IgG Ab reactivity against HLA-E and anti-HLA-G HCs, respectively. Evidently, anti-HLA-F HC Abs are the most predominant anti-HLA-Ib HC IgG Abs in RA patients. The incidence and intensity of Abs against HLA-E, HLA-F, and HLA-G in the normal control group were much higher than those observed in RA patients. Evidently, the lower level of Abs in RA patients points to the impact of the immunosuppressive drugs on these patients. These results underscore the need for further studies to unravel the nature of HLA-F variants on activated immune cells and synoviocytes of RA patients. Full article
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Review

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21 pages, 354 KiB  
Review
Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes
by Lindsay E. Bass and Rachel H. Bonami
Antibodies 2024, 13(2), 27; https://doi.org/10.3390/antib13020027 - 1 Apr 2024
Viewed by 2874
Abstract
Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells [...] Read more.
Islet autoantibodies predict type 1 diabetes (T1D) but can be transient in murine and human T1D and are not thought to be directly pathogenic. Rather, these autoantibodies signal B cell activity as antigen-presenting cells (APCs) that present islet autoantigen to diabetogenic T cells to promote T1D pathogenesis. Disrupting B cell APC function prevents T1D in mouse models and has shown promise in clinical trials. Autoantigen-specific B cells thus hold potential as sophisticated T1D biomarkers and therapeutic targets. B cell receptor (BCR) somatic hypermutation is a mechanism by which B cells increase affinity for islet autoantigen. High-affinity B and T cell responses are selected in protective immune responses, but immune tolerance mechanisms are known to censor highly autoreactive clones in autoimmunity, including T1D. Thus, different selection rules often apply to autoimmune disease settings (as opposed to protective host immunity), where different autoantigen affinity ceilings are tolerated based on variations in host genetics and environment. This review will explore what is currently known regarding B cell signaling, selection, and interaction with T cells to promote T1D pathogenesis. Full article
18 pages, 1032 KiB  
Review
Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies
by Vitaly Chasov, Ekaterina Zmievskaya, Irina Ganeeva, Elvina Gilyazova, Damir Davletshin, Marat Khaliulin, Emmanuel Kabwe, Yuriy N. Davidyuk, Aygul Valiullina, Albert Rizvanov and Emil Bulatov
Antibodies 2024, 13(1), 10; https://doi.org/10.3390/antib13010010 - 1 Feb 2024
Cited by 8 | Viewed by 5906
Abstract
Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including the interferon signature, loss of [...] Read more.
Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed, including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis, such as B cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc. Here, we overview novel therapeutic approaches based on CAR-T cells and antibodies for targeting systemic autoimmune diseases. Full article
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14 pages, 658 KiB  
Review
Antiphospholipid Antibodies Associated with Native Arteriovenous Fistula Complications in Hemodialysis Patients: A Comprehensive Review of the Literature
by Maxime Taghavi, Abla Jabrane, Lucas Jacobs, Maria Do Carmo Filomena Mesquita, Anne Demulder and Joëlle Nortier
Antibodies 2024, 13(1), 1; https://doi.org/10.3390/antib13010001 - 2 Jan 2024
Cited by 2 | Viewed by 2705
Abstract
Antiphospholipid antibody (aPL)-persistent positivity is frequent in hemodialysis (HD) patients. Native arteriovenous fistula (AVF) complications such as stenosis and thrombosis are among the most important causes of morbidity and mortality in hemodialysis patients. The association between aPL positivity and AVF thrombosis seems to [...] Read more.
Antiphospholipid antibody (aPL)-persistent positivity is frequent in hemodialysis (HD) patients. Native arteriovenous fistula (AVF) complications such as stenosis and thrombosis are among the most important causes of morbidity and mortality in hemodialysis patients. The association between aPL positivity and AVF thrombosis seems to now be well established. However, whether aPL positivity is associated with other AVF complications, such as maturation failure or stenosis, is not well known. Given the significant impact of AVF failure on patient’s prognosis, it is of interest to further investigate this particular point in order to improve prevention, surveillance and treatment, and, ultimately, the patient’s outcome. This literature review aims to report the recent literature on aPL-associated native AVF complications. Full article
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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 8 | Viewed by 7887
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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Other

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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 2602
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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