Advances in Autoimmune and Rheumatic Diseases: A Theme Issue in Honor of Prof. Dr. Yehuda Shoenfeld

A special issue of Immuno (ISSN 2673-5601).

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 38946

Special Issue Editors

Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
Interests: immunology of rheumatic disorders and COVID-19; vascular immunology; pathophysiology of vasculitis and atherosclerosis; auto-immunity to myeloïd lysosomal enzymes (ANCA); pathophysiology of foreign-body induced autoimmunity; ASIA (Shoenfeld's) syndrome; role of vitamin D in auto-immune diseases
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Rheumatology, Department of Medicine and Surgery, University of Perugia, p.le Menghini 1, 06129 Perugia, Italy
Interests: inflammatory arthritis; connective tissue diseases; systemic lupus erythematosus; Sjogren's syndrome; rare diseases in rheumatology
Special Issues, Collections and Topics in MDPI journals
CNRS UMR7242, Biotechnology and Cell Signaling/Strasbourg Drug Discovery and Development Institute (IMS), University of Strasbourg, 67000 Strasbourg, France
Interests: immunology; inflammation; autoimmunity; molecular therapy; immunopeptide; peptide delivery; autophagy; cytokines/chemokines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Prof. Yehuda Shoenfeld is undoubtedly the father of modern autoimmunity. His pioneering studies spaced over a magnitude of branches of immunity, from systemic lupus erythematosus, anti-phospholipid syndrome and COVID-19/SARS-CoV-2 to the identification of environmental and genetic factors contributing to autoimmunity depicting—and first coining—the term “mosaic of autoimmunity”.

Prof. Yehuda Shoenfeld is the founder of the Zabludowicz Center for Autoimmune Diseases, at the Sheba Medical Center, which is affiliated to the Sackler Faculty of Medicine in Tel-Aviv University, in Israel; he is the incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases at the Tel-Aviv University. He is the head of the Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint-Petersburg, Russian Federation, and a visiting professor at Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation.

His clinical and scientific works have focused on autoimmune and rheumatic diseases, and he has published more than 2200 papers in journals such as The New England Journal of Medicine, Nature, Lancet, Proceedings of the National Academy of Sciences of the United States of America, Journal of Clinical Investigation, Journal of Immunology, Blood, FASEB, Journal of Experimental Medicine, Circulation, and Cancer. His articles have had over 125,000 citations. He has written more than four hundred chapters in books, and has authored and edited 100 books, some of which have become cornerstones in science and clinical practice, such as "The Mosaic of Autoimmunity"; "Infections and Autoimmunity"; and the textbooks "Autoantibodies" and "Diagnostic criteria of autoimmune diseases". He is on the editorial board of over 40 journals in the field of rheumatology and autoimmunity, and is the founder and the editor of the IMAJ (Israel Medical Association Journal), the representative journal of science and medicine in the English language in Israel, and is also the founder and editor of "Autoimmunity Reviews" (Elsevier) and co-editor of "Journal of Autoimmunity". He has organized over 20 international congresses in autoimmunity.

Prof. Shoenfeld received the EULAR prize in 2005, in Vienna, Austria, for his article "The infectious etiology of anti-phospholipid syndrome". He received a gold medal from the Slovak Society of Physicians for his contribution to the Israel–Slovakia collaboration (March 2006) and is an honorary member of the Hungarian Association of Rheumatology. At UC Davis, USA, Dr. Shoenfeld received the Nelson's Prize for Humanity and Science in 2008. In 2009, he was honored as Doctoris Honoris Causa at Debrecen University (Hungary); since 2009, he has also been an honorary member of the Slovenian National Academy of Sciences. He has been awarded a Life Contribution Prize in Internal Medicine in Israel in 2012, as well as the ACR Master Award in 2013. He is also a member of the Israeli Academy of Science.

He has been the mentor of the mentors, since he has trained generations of immunologists striving and succeeding in the generation of the family of autoimmunity. His knowledge is only paired by his generosity, his intuition by his humanity.

Immuno is highly pleased to host a Themed Issue honoring Prof. Yehuda Shoenfeld for his outstanding achievements in advancing the field of autoimmunity.

Immuno invites scientists to submit original contributions to:

“Mosaic of Autoimmunity”: A Theme Issue in Honor of Prof. Dr. Yehuda Shoenfeld.

Please join us in collectively congratulating him for his outstanding accomplishments.

Prof. Dr. Jan Willem Cohen Tervaert
Dr. Carlo Perricone
Prof. Dr. Sylviane Muller
Guest Editors

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Published Papers (7 papers)

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Research

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13 pages, 4988 KiB  
Article
Vitamin D Receptor and Its Influence on Multiple Sclerosis Risk and Severity: From Gene Polymorphisms to Protein Expression
by Cristiana Pistono, Cecilia Osera, Maria Cristina Monti, Chiara Boiocchi, Giulia Mallucci, Mariaclara Cuccia, Cristina Montomoli, Roberto Bergamaschi and Alessia Pascale
Immuno 2022, 2(3), 469-481; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2030029 - 27 Jul 2022
Cited by 3 | Viewed by 2209
Abstract
Multiple sclerosis (MS) is a multifactorial neurodegenerative disease. Low levels of vitamin D are a risk factor for MS and alterations in the vitamin D receptor (VDR) might be a risk factor as well. This study aimed to evaluate whether the [...] Read more.
Multiple sclerosis (MS) is a multifactorial neurodegenerative disease. Low levels of vitamin D are a risk factor for MS and alterations in the vitamin D receptor (VDR) might be a risk factor as well. This study aimed to evaluate whether the VDR rs731236 (Taq-I) and rs4334089 (HpyCH4V) gene polymorphisms and VDR protein expression are associated with MS risk and severity. Vitamin D plasma levels were analyzed in a group of patients. Additional analyses of VDR protein expression and vitamin D levels of patients with different forms of MS (MSSS < 3 and MSSS ≥ 3) were performed. The analysis of the genotypic and allelic frequencies revealed that the rs731236 (Taq-I) gene polymorphism is significantly associated with MS presence. Although the total, cytosolic and nuclear VDR protein contents do not change between MS patients and healthy controls and between patients with different MS severity, vitamin D levels decrease in parallel with an increase in MSSS. Full article
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16 pages, 2805 KiB  
Article
Geographic Location Determines Differentially Methylated Gene Expressions in Autoimmune Diseases
by Jacques-Olivier Pers, Hajar Bahane, Christelle Le Dantec, Nathan Foulquier, Marta E. Alarcon-Riquelme, Pierre Youinou and PRECISESADS Clinical Consortium
Immuno 2021, 1(4), 529-544; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno1040037 - 01 Dec 2021
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Abstract
Further observations support the role of environmental factors in autoimmune diseases via the alteration of the epigenetic machinery. In this context, ultraviolet light, smoking, chemicals, and psychological stress have been described as likely examples of this phenomenon. For this study, we took advantage [...] Read more.
Further observations support the role of environmental factors in autoimmune diseases via the alteration of the epigenetic machinery. In this context, ultraviolet light, smoking, chemicals, and psychological stress have been described as likely examples of this phenomenon. For this study, we took advantage of the PRECISESADS IMI project, which gathered joint data from 2500 individuals with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), primary antiphospholipid syndrome (PAPS), and mixed connective tissue disease (MCTD), and aimed to determine such epigenetic modifications in SLE, SSc, pSS, and RA patients. Here, we performed a set of measures in several countries from the north and south of Europe. We observed that autoimmune patients from the north of Europe presented a higher hypomethylated profile associated with an increased gene expression than patients from the south. These genes were associated with interferon (IFN) pathways, immunity, and the pathways associated with cellular metabolism. Since the IFN scores were increased in this population, these patients presented a more inflammatory profile. To conclude, the geographical location of patients with autoimmune diseases has an impact on DNA methylation, RNA expression, and immunological profiles. Full article
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25 pages, 1824 KiB  
Review
Predisposing Factors, Clinical Picture, and Outcome of B-Cell Non-Hodgkin’s Lymphoma in Sjögren’s Syndrome
by Ioanna E. Stergiou, Andreas V. Goules, Michael Voulgarelis and Athanasios G. Tzioufas
Immuno 2022, 2(4), 584-608; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2040037 - 20 Oct 2022
Cited by 1 | Viewed by 3446
Abstract
Among other systemic autoimmune diseases, primary Sjögren syndrome (pSS) bears the highest risk for lymphoma development. In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell [...] Read more.
Among other systemic autoimmune diseases, primary Sjögren syndrome (pSS) bears the highest risk for lymphoma development. In pSS, chronic antigenic stimulation gradually drives the evolution from polyclonal B-cell expansion to oligoclonal/monoclonal B-cell predominance to malignant B-cell transformation. Thus, most pSS-related lymphomas are B-cell non-Hodgkin lymphomas (NHLs), with mucosa-associated lymphoid tissue (MALT) lymphomas predominating, followed by diffuse large B-cell lymphomas (DLBCLs) and nodal marginal zone lymphomas (NMZLs). Since lymphomagenesis is one of the most serious complications of pSS, affecting patients’ survival, a plethora of possible predisposing factors has been studied over the years, ranging from classical clinical, serological, hematological, and histological, to the more recently proposed genetic and molecular, allowing clinicians to timely detect and to closely follow-up the subgroup of pSS patients with increased risk for lymphoma development. Overall predisposing factors for pSS-related lymphomagenesis reflect the status of B-cell hyperactivity. Different clinical features have been described for each of the distinct pSS-related B-cell NHL subtypes. While generally pSS patients developing B-cell NHLs display a fairly good prognosis, outcomes in terms of treatment response and survival rates seem to differ depending on the lymphoma subtype, with MALT lymphomas being characterized by a rather indolent course and DLBCLs gravely affecting patients’ survival. Full article
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14 pages, 709 KiB  
Review
The Role of T Cells in Systemic Sclerosis: An Update
by Lazaros I. Sakkas and Dimitrios P. Bogdanos
Immuno 2022, 2(3), 534-547; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2030034 - 13 Sep 2022
Cited by 1 | Viewed by 3519
Abstract
Systemic sclerosis (SSc) is a chronic disease characterized by microvasculopathy, autoantibodies (autoAbs), and fibrosis. The pathogenesis of the disease is incompletely understood. Microvasculopathy and autoAbs appear very early in the disease process. AutoAbs, such as those directed against DNA topoisomerase I (Topo I), [...] Read more.
Systemic sclerosis (SSc) is a chronic disease characterized by microvasculopathy, autoantibodies (autoAbs), and fibrosis. The pathogenesis of the disease is incompletely understood. Microvasculopathy and autoAbs appear very early in the disease process. AutoAbs, such as those directed against DNA topoisomerase I (Topo I), are disease specific and associated with disease manifestations, and indicate activation of the adaptive immune system. B cells are involved in fibrosis in SSc. T cells are also involved in disease pathogenesis. T cells show signs of antigen-induced activation; T cells of TH2 type are increased and produce profibrotic cytokines interleukin (IL)-4, IL-13, and IL-31; CD4+ cytotoxic T lymphocytes are increased in skin lesions, and cause fibrosis and endothelial cell apoptosis; circulating T follicular helper (TFH) cells are increased in SSc produce IL-21 and promote plasmablast antibody production. On the other hand, regulatory T cells are impaired in SSc. These findings provide strong circumstantial evidence for T cell implication in SSc pathogenesis and encourage new T cell-directed therapeutic strategies for the disease. Full article
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14 pages, 1475 KiB  
Review
CIDP: Current Treatments and Identification of Targets for Future Specific Therapeutic Intervention
by Susana Brun, Jérôme de Sèze and Sylviane Muller
Immuno 2022, 2(1), 118-131; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2010009 - 21 Jan 2022
Cited by 3 | Viewed by 17039
Abstract
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. This clinically heterogeneous neurological disorder is closely related to Guillain–Barré syndrome and is considered the chronic counterpart of that acute disease. Currently available treatments are mostly empirical; [...] Read more.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. This clinically heterogeneous neurological disorder is closely related to Guillain–Barré syndrome and is considered the chronic counterpart of that acute disease. Currently available treatments are mostly empirical; they include corticosteroids, intravenous immunoglobulins, plasma exchange and chronic immunosuppressive agents, either alone or in combination. Recent advances in the understanding of the underlying pathogenic mechanisms in CIDP have brought a number of novel ways of possible intervention for use in CIDP. This review summarizes selected pre-clinical and clinical findings, highlights the importance of using adapted animal models to evaluate the efficacy of novel treatments, and proposes the outlines of future directions to ameliorate the conditions of patients with CIDP. Full article
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19 pages, 1091 KiB  
Review
Polymorphonuclear Neutrophils in Rheumatoid Arthritis and Systemic Lupus Erythematosus: More Complicated Than Anticipated
by Ahmad Haidar Ahmad, Dyhia Melbouci and Patrice Decker
Immuno 2022, 2(1), 85-103; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2010007 - 07 Jan 2022
Cited by 3 | Viewed by 5200
Abstract
Polymorphonuclear neutrophils (PMN) are the most abundant leucocytes in the circulation in humans. They represent a heterogeneous population exerting diverse functions through several activities. Usually described as typical pro-inflammatory cells, immunomodulatory properties of PMNs have been reported. Among others, once activated and depending [...] Read more.
Polymorphonuclear neutrophils (PMN) are the most abundant leucocytes in the circulation in humans. They represent a heterogeneous population exerting diverse functions through several activities. Usually described as typical pro-inflammatory cells, immunomodulatory properties of PMNs have been reported. Among others, once activated and depending on the stimulus, PMNs expel neutrophil extracellular traps (NET) in the extracellular space. NETs are complexes made of DNA and granule proteins representing an innate immune mechanism fighting infections. Nevertheless, an excess of NET formation might be involved in the development of inflammatory or autoimmune responses. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two chronic, inflammatory, autoimmune diseases of unknown etiology and affecting mostly women. Several abnormal or non-classical functions of PMNs or PMN sub-populations have been described in SLE and RA. Particularly, NETs have been suggested to trigger pro-inflammatory responses by exposing pro-inflammatory mediators. Likewise, NETs may be the targets of autoantibodies or even might trigger the development of autoantibodies by exposing autoantigens. In the present review, we will summarize heterogeneous properties of human PMNs and we will discuss recent evidence linking PMNs and NETs to the pathogenesis of both SLE and RA. Full article
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12 pages, 474 KiB  
Review
Vitamin D Immune-Mediated Responses and SARS-CoV-2 Infection: Clinical Implications in COVID-19
by Emanuele Gotelli, Sabrina Paolino, Stefano Soldano and Maurizio Cutolo
Immuno 2022, 2(1), 1-12; https://0-doi-org.brum.beds.ac.uk/10.3390/immuno2010001 - 24 Dec 2021
Cited by 1 | Viewed by 3211
Abstract
Active vitamin D is a true steroid hormone with pleiotropic biological effects that go beyond the classical concept of bone metabolism regulation. In fact, adequate serum levels of 25-hydroxyvitamin D (>40 ng/mL) are required to support several biological functions, including the control of [...] Read more.
Active vitamin D is a true steroid hormone with pleiotropic biological effects that go beyond the classical concept of bone metabolism regulation. In fact, adequate serum levels of 25-hydroxyvitamin D (>40 ng/mL) are required to support several biological functions, including the control of innate and adaptive immunity in course of infectious, inflammatory and autoimmune diseases. SARS-CoV-2 is responsible for the COVID-19 pandemic and deficient/insufficient serum levels of 25-hydroxyvitamin D are reported in very large cohorts of patients. Of note, vitamin D is involved in different pathophysiological processes, such as expression of SARS-CoV-2 receptor (ACE2), activation of innate (neutrophils with their extracellular traps, monocytes/macrophages, dendritic cells, natural killer cells) and adaptive (T and B lymphocytes) immune cells and clinical manifestations, such as coagulation/thrombotic disorders and acute respiratory distress syndrome. Randomized clinical trials regarding vitamin D supplementation in COVID-19 patients have shown favorable effects on the control of inflammation markers, arterial oxygen saturation/inspired fraction of oxygen ratio, admission to hospital intensive care units and mortality. A target of serum 25-hydroxyvitamin D > 50 ng/mL has been identified as protective for the course of COVID-19, potentially playing an ancillary role in the treatment of the disease. Full article
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