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Biomolecules
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Emerging Molecular Targets in Sjogren’s Syndrome
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Emerging Molecular Targets in Sjogren’s Syndrome

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 25019

Special Issue Editors

Prof. Dr. Roberto Gerli

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Guest Editor
Rheumatology, Department of Medicine, University of Perugia, Piazzale Menghini 1, 06129 Perugia, Italy
Interests: T lymphocytes; rheumatoid arthritis; systemic lupus erythematosus; autoantibodies; autoimmunity
Special Issues, Collections and Topics in MDPI journals
Dr. Carlo Perricone

E-Mail Website
Guest Editor
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
Dr. Elena Bartoloni

E-Mail Website
Guest Editor
Associate Professor, Rheumatology, Department of Medicine, University of Perugia, Piazzale Menghini 1, 06129 Perugia, Italy
Interests: Sjögren’s syndrome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sjogren’s syndrome (SjS) is an autoimmune inflammatory lymphoproliferative disease in which genetic and environmental factors play a fundamental role, causing the dysfunction of T cells, B cells, and the production of autoantibodies. The inflammatory process in SjS affects exocrine glands, particularly salivary glands. Genome-wide association studies have identified numerous loci that may harbor susceptibility genes, although the functional significance of most of these polymorphisms remains currently unknown. In addition to the impact of the human leukocyte antigen locus, the best-characterized genes codify for molecules involved in different immunological pathways, including the signal transducer and activator of transcription 4, mainly implicated in Th17 activation and differentiation, and the interferon regulatory factor, which is involved in type 1 interferon signaling. Endogenous retroviruses have long been implicated in triggering autoimmunity through structural and functional molecular mimicry with viral proteins. Autoantibodies are a hallmark of the disease and may depict specific clinical phenotypes. Current therapies largely rely on the use of corticosteroids and immunosuppressants. Interference with pro-inflammatory cytokines and mechanisms that link innate and adaptive immunity offers new options in the treatment of SjS. There are several intriguing approaches, for instance, directed against Toll-like receptors, the inflammasome chemokines or through inhibition of apoptosis, which are emerging and directed at preserving and restoring functional exocrine tissue. A rational approach for therapeutic design requires a detailed understanding of disease pathogenesis, and the chance to use biological and targeted synthetic DMARDs represents an emerging new era for patients with SjS.

Potential topics include but are not limited to the following:

  • The role of genetics in the pathogenesis of SjS;
  • Biomarkers and SjS;
  • T cells in SjS;
  • Autoantibodies in SjS;
  • Novel potential compounds in SjS;
  • Emerging new strategies for the treatment of patients with SjS.

Papers are published upon acceptance, regardless of the Special Issue publication date.

The deadline for submission is December 31s2020

Regarding the formatting, reviews, original articles, and brief articles are acceptable.

There are no restrictions in the length of manuscripts, but the text should be concise and comprehensive. If possible, the abstract should be limited to 250 words, and we ask you to provide 3–10 keywords for future indexing. Review papers should contain at least 3500 words text in the main body. References should be up-to-date. We suggest including at least one summative table or figure in the manuscript.

Prof. Roberto Gerli
Dr. Carlo Perricone
Prof. Elena Bartoloni
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

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13 pages, 1920 KiB  
Article
Cognitive Impairment, Sleep Disturbance, and Depression in Women with Silicone Breast Implants: Association with Autoantibodies against Autonomic Nervous System Receptors
by Milena Tocut, Gilad Halpert, Avishai M. Tsur, Kassem Sharif, Harald Heidecke, Yair Levy, Abdulla Watad, Howard Amital and Yehuda Shoenfeld
Biomolecules 2022, 12(6), 776; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12060776 - 02 Jun 2022
Cited by 6 | Viewed by 2435
Abstract
Background: Silicone breast implants (SBIs) has been shown to be associated with an increased risk of autoimmune diseases. In the current study, we aimed to explore the potential association between circulating autoantibodies against the autonomic nervous system and cognitive impairment, memory deficit, and [...] Read more.
Background: Silicone breast implants (SBIs) has been shown to be associated with an increased risk of autoimmune diseases. In the current study, we aimed to explore the potential association between circulating autoantibodies against the autonomic nervous system and cognitive impairment, memory deficit, and depressive symptoms reported by women with SBIs. Methods: ELISA assays were used to quantify anti-adrenergic receptors (α1, α2, β1, β2), anti-muscarinic receptors (M1-M5), anti-endothelin receptor type A, and anti-angiotensin II type 1 receptor titers in the sera of 93 symptomatic female subjects with SBIs and 36 age-matched healthy female controls. Results: A significant difference was detected in the level of autoantibodies against the autonomic nervous system receptors in women with SBIs who reported memory impairment, cognitive impairment, and sleep disturbance as compared with both women with SBIs who did not complain of these symptoms or with healthy individuals without SBIs. Conclusions: Clinical symptoms such as depression, cognitive impairment, and sleep disturbances were found to be associated with dysregulation of the levels of circulating autoantibodies targeting the autonomous nervous system receptors in women with SBIs. These autoantibodies may have diagnostic significance in diseases associated with breast implants. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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Review

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13 pages, 655 KiB  
Review
Instruments for Outcome Evaluation of Specific Domains in Primary Sjögren’s Syndrome
by Nicoletta Del Papa, Antonina Minniti, Wanda Maglione, Francesca Pignataro, Roberto Caporali and Claudio Vitali
Biomolecules 2021, 11(7), 953; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11070953 - 28 Jun 2021
Cited by 1 | Viewed by 2164
Abstract
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder characterized by very heterogeneous features. The spectrum of this disorder may vary from benign but disabling symptoms such as dryness, due to lachrymal and salivary involvement, pain and fatigue, to systemic, potentially severe, manifestations [...] Read more.
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder characterized by very heterogeneous features. The spectrum of this disorder may vary from benign but disabling symptoms such as dryness, due to lachrymal and salivary involvement, pain and fatigue, to systemic, potentially severe, manifestations that may involve any organ. In recent decades, the arrival of biotechnological therapy has offered new opportunities for the treatment of this—until now—orphan disease. Currently, the possible use of these new drugs in therapeutic trials has made it necessary to have reliable outcome measures to evaluate their efficacy in this disease. A great effort has been made in multicenter, often multinational, studies to develop and validate instruments capable of assessing the different disease-related features. The adoption in therapeutic trials of the newly developed outcome measures aimed at assessing systemic features and patient reported symptoms has often yielded disappointing results. These negative data have been ascribed, on the one hand, to the trial design not being completely appropriate, and, on the other hand, to the fact that a single instrument may be not sufficient to cover the great clinical heterogeneity of the disease features. There is now growing belief that composite end points that include instruments that are able to assess the various aspects of the disease may be more properly and successfully used in future therapeutic trials. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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15 pages, 1400 KiB  
Review
The Role of Interferons in the Pathogenesis of Sjögren’s Syndrome and Future Therapeutic Perspectives
by Nicoletta Del Papa, Antonina Minniti, Maurizio Lorini, Vincenzo Carbonelli, Wanda Maglione, Francesca Pignataro, Nicola Montano, Roberto Caporali and Claudio Vitali
Biomolecules 2021, 11(2), 251; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11020251 - 09 Feb 2021
Cited by 24 | Viewed by 3642
Abstract
There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren’s syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type [...] Read more.
There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren’s syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the ‘so-called’ type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression. The role of type II (IFNγ) in this subset of pSS patients, together with the potentially related activation of completely different immunological and metabolic pathways, are emerging issues. Expression of both types of IFNs has also been shown in target tissues, namely in minor salivary glands where a predominance of type II IFN signature appeared to have a certain association with the development of lymphoma. In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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13 pages, 1395 KiB  
Review
Immune Monitoring upon Treatment with Biologics in Sjögren’s Syndrome: The What, Where, When, and How
by Joyce J.B.C. van Beers and Jan G.M.C. Damoiseaux
Biomolecules 2021, 11(1), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11010116 - 16 Jan 2021
Cited by 4 | Viewed by 2906
Abstract
Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target [...] Read more.
Over the years, a wide variety of therapeutic antibodies has been successfully introduced in the auto-immunology clinic, and many more are on the way. Many of these treatments address either a pathogenic circulating molecule or a cell-bound molecule. Whereas addressing the former target results in neutralization of the soluble factor and binding to the latter target either inhibits cellular function or induces selective cell death. If this targeted molecule or cell is part of the immune system, this therapy evokes a state of immunodeficiency with infections as a possible consequence. Therefore, immune monitoring is needed to prevent such adverse side effects of immunotherapy. In this paper, different immunotherapies used in Sjögren’s syndrome, as well as different approaches to monitoring the immune system, are discussed. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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19 pages, 1176 KiB  
Review
T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome
by William de Jesús Ríos-Ríos, Sorely Adelina Sosa-Luis and Honorio Torres-Aguilar
Biomolecules 2020, 10(11), 1539; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10111539 - 11 Nov 2020
Cited by 22 | Viewed by 3188
Abstract
Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different [...] Read more.
Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different stages of the ailment, becoming involved in specific pathologic roles. Initially, their activated phenotype endows them with high migratory properties and increased pro-inflammatory cytokine secretion in target tissues. Later, the accumulation of immunomodulatory T cells-derived factors, such as IL-17, IFN-γ, or IL-21, preserve the inflammatory environment. These effects favor strong B cell activation, instigating an extrafollicular antibody response in ectopic lymphoid structures mediated by T follicular helper cells (Tfh) and leading to disease progression. Additionally, the memory effector phenotype of CD8+ T cells present in SS patients suggests that the presence of auto-antigen restricted CD8+ T cells might trigger time-dependent and specific immune responses. Regarding the protective roles of traditional regulatory T cells (Treg), uncertain evidence shows decrease or invariable numbers of circulating and infiltrating cells. Nevertheless, an emerging Treg subset named follicular regulatory T cells (Tfr) seems to play a critical protective role owing to their deficiency that enhances SS development. In this review, the authors summarize the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues, and that simultaneously make them key therapeutic targets for SS treatment. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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16 pages, 987 KiB  
Review
Classical Examples of the Concept of the ASIA Syndrome
by Vânia Borba, Anna Malkova, Natalia Basantsova, Gilad Halpert, Laura Andreoli, Angela Tincani, Howard Amital and Yehuda Shoenfeld
Biomolecules 2020, 10(10), 1436; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10101436 - 12 Oct 2020
Cited by 45 | Viewed by 9760
Abstract
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, [...] Read more.
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria. Full article
(This article belongs to the Special Issue Emerging Molecular Targets in Sjogren’s Syndrome)
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