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IJMS
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Molecular Research on Systemic Sclerosis: From Pathogenesis to Management
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Molecular Research on Systemic Sclerosis: From Pathogenesis to Management

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4590

Special Issue Editors

Dr. Elisabetta Zanatta

E-Mail Website
Guest Editor
Department of Medicine (DIMED), University Hospital of Padova, 35126 Padova, Italy
Interests: systemic sclerosis; autoantibodies; interstitial lung disease; pulmonary arterial hypertension; coronary microvascular disease; target therapies
Dr. Corrado Campochiaro

E-Mail Website
Guest Editor
IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy
Interests: systemic sclerosis; targeted treatments; interstitial lung disease; digital ulcers; calcinosis; pulmonary arterial hypertension; autoantibodies; progression; disease outcomes; Takayasu arteritis; giant cell arteritis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, new intriguing pathogenic pathways have emerged in Systemic Sclerosis (SSc). Their knowledge allows for a better stratification of the disease phenotype and a prediction of response of targeted-specific treatments in this rare systemic connective tissue disease. The discovery of new pathogenic pathways has indeed revolutionized the SSc world and has led to the approval of the first targeted-oriented drugs in SSc.

In this Special Issue for IJMS, we will focus on the new insights in the pathogenesis and management of SSc, particularly at molecular research level. Our aim is to provide new evidence that will help to improve the therapeutic approach to this complex disease, moving towards precision medicine.

Research papers and up-to-date review articles are all welcome.

Dr. Elisabetta Zanatta
Dr. Corrado Campochiaro
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • systemic sclerosis
  • molecular research
  • pathogenesis
  • microangiopathy
  • interstitial lung disease
  • pulmonary arterial hypertension
  • disease phenotype
  • treatment

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Published Papers (2 papers)

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Research

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13 pages, 2804 KiB  
Article
Immune Profiling of Patients with Systemic Sclerosis through Targeted Proteomic Analysis
by Iulia Szabo, Medeea Badii, Ildikó O. Gaál, Robert Szabo, Claudia Sîrbe, Oana Humiță, Leo A. B. Joosten, Tania O. Crișan and Simona Rednic
Int. J. Mol. Sci. 2023, 24(24), 17601; https://doi.org/10.3390/ijms242417601 - 18 Dec 2023
Viewed by 1767
Abstract
High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease [...] Read more.
High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease endotypes using circulating proteins, and determine the diagnostic performance of significantly expressed plasma analytes. We performed targeted proteomic profiling in a cohort of fifteen patients with SSc and eighteen controls using the Olink® (Olink Bioscience, Uppsala, Sweden)Target 96 Inflammation Panels. Seventeen upregulated proteins involved in angiogenesis, innate immunity, and co-stimulatory pathways discriminated between patients with SSc and healthy controls (HCs) and further classified them into two clusters, a low-inflammatory and a high-inflammatory endotype. Younger age, shorter disease duration, and lack of reflux esophagitis characterized patients in the low-inflammatory endotype. TNF, CXCL9, TNFRSF9, and CXCL10 positively correlated with disease progression, while the four-protein panel comprising TNF, CXCL9, CXCL10, and CX3CL1 showed high diagnostic performance. Collectively, this study identified a distinct inflammatory signature in patients with SSc that reflects a persistent T helper type 1 (Th 1) immune response irrespective of disease duration, while the multi-protein panel might improve early diagnosis in SSc. Full article
(This article belongs to the Special Issue Molecular Research on Systemic Sclerosis: From Pathogenesis to Management)
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Review

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17 pages, 983 KiB  
Review
Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis
by Marco Binda, Beatrice Moccaldi, Giovanni Civieri, Anna Cuberli, Andrea Doria, Francesco Tona and Elisabetta Zanatta
Int. J. Mol. Sci. 2024, 25(4), 2299; https://doi.org/10.3390/ijms25042299 - 15 Feb 2024
Cited by 2 | Viewed by 2356
Abstract
Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery [...] Read more.
Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery of functional antibodies targeting G-protein-coupled receptors (GPCRs), whose presence has been demonstrated in different autoimmune conditions, has shed some light on SSc pathogenesis. These antibodies bind to GPCRs expressed on immune and non-immune cells as their endogenous ligands, exerting either a stimulatory or inhibitory effect on corresponding intracellular pathways. Growing evidence suggests that, in SSc, the presence of anti-GPCRs antibodies correlates with specific clinical manifestations. Autoantibodies targeting endothelin receptor type A (ETAR) and angiotensin type 1 receptor (AT1R) are associated with severe vasculopathic SSc-related manifestations, while anti-C-X-C motif chemokine receptors (CXCR) antibodies seem to be predictive of interstitial lung involvement; anti-muscarinic-3 acetylcholine receptor (M3R) antibodies have been found in patients with severe gastrointestinal involvement and anti-protease-activated receptor 1 (PAR1) antibodies have been detected in patients experiencing scleroderma renal crisis. This review aims to clarify the potential pathogenetic significance of GPCR-targeting autoantibodies in SSc, focusing on their associations with the different clinical manifestations of scleroderma. An extensive examination of functional autoimmunity targeting GPCRs might provide valuable insights into the underlying pathogenetic mechanisms of SSc, thus enabling the development of novel therapeutic strategies tailored to target GPCR-mediated pathways. Full article
(This article belongs to the Special Issue Molecular Research on Systemic Sclerosis: From Pathogenesis to Management)
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