International Journal of Molecular Sciences

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Special Issue Editors

Dr. Elisabetta Zanatta

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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

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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
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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

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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.

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Keywords

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

Published Papers (2 papers)

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Research

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13 pages, 2804 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417601 - 18 Dec 2023

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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 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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/ijms25042299 - 15 Feb 2024

Viewed by 1271

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 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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