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Novel Diagnostic and Therapeutic Perspectives in Systemic Sclerosis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology & Rheumatology".

Deadline for manuscript submissions: 15 June 2026 | Viewed by 89

Special Issue Editor


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Guest Editor
1. Department of Internal Medicine, Division of Rheumatology, Allergology and Clinical Immunology, University Hospital of Split, 21000 Split, Croatia
2. Internal Medicine Department, School of Medicine, University of Split, 21000 Split, Croatia
Interests: connective tissue diseases; rheumatoid arthritis; psoriatic disease; cardiorheumatology; interstitial lung disease; pulmonary arterial hypertension; microcirculation in rheumatic diseases
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Special Issue Information

Dear Colleagues,

Early diagnosis and treatment of systemic sclerosis are advancing through a mechanistic understanding of vasculopathy, immune dysregulation, and fibrosis. Diagnostic improvements include VEDOSS criteria, autoantibody biomarkers, advanced imaging, and nailfold capillaroscopy for early detection. Targeted therapies, such as mycophenolate mofetil, nintedanib, tocilizumab, and rituximab, are emerging, with autologous stem cell transplantation being considered for select patients.

Personalized, biomarker-driven therapies targeting immune, vascular, and fibrotic pathways are under development. CD19 CAR-T cell therapy, bsAbs, and novel agents targeting interferon pathways, BAFF, FcRn, and pro-fibrotic signaling represent a shift towards precision medicine and immune reprogramming. These are promising for patients with early diffuse disease or refractory complications.

Early intervention and cross-organ treatment strategies offer potential for disease modification beyond symptom management. The critical goal is validating early biomarkers of disease trajectory and incorporating them into treatment algorithms to enable personalized and preventive strategies. This necessitates adaptive, mechanism-based trial designs to accelerate the implementation of novel therapies.

Dr. Mislav Radić
Guest Editor

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Keywords

  • systemic sclerosis
  • biomarkers
  • diagnosis
  • treatment
  • diagnostic imaging technique
  • early detection

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Published Papers (1 paper)

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Review

19 pages, 581 KB  
Review
Anifrolumab—A Potential New Systemic Sclerosis Treatment
by Mislav Radić, Petra Šimac Prižmić, Tina Bečić, Hana Đogaš, Dijana Perković, Josipa Radić and Damir Fabijanić
J. Clin. Med. 2026, 15(3), 1104; https://doi.org/10.3390/jcm15031104 - 30 Jan 2026
Abstract
Background/Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by chronic inflammation, microvascular injury, and fibrosis of the skin and internal organs. Although there are therapies, there is a need for treatments targeting early pathogenic mechanisms. Type I interferons (IFN-I) are key [...] Read more.
Background/Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by chronic inflammation, microvascular injury, and fibrosis of the skin and internal organs. Although there are therapies, there is a need for treatments targeting early pathogenic mechanisms. Type I interferons (IFN-I) are key mediators linking immune dysregulation to vascular and fibrotic damage in SSc. This review summarizes the current evidence supporting IFN-I blockade with anifrolumab as a novel therapeutic strategy. Methods: A narrative review of preclinical, translational, and emerging clinical studies was conducted to evaluate the role of IFN-I signaling in SSc and the therapeutic potential of anifrolumab. Particular focus was placed on the IFN signature, upregulation of interferon-stimulated genes (ISGs), and the association with disease activity and organ involvement. Results: Anifrolumab, a fully human monoclonal antibody targeting the IFN-I receptor subunit 1 (IFNAR1), inhibits the signaling of all IFN-I isoforms, suppressing downstream JAK–STAT activation and ISG expression. Mechanistic data suggest that IFNAR blockade modulates vascular injury, immune activation, and fibrosis. Early findings and ongoing trials indicate potential benefits, particularly in patients with a high IFN signature or rapidly progressive cutaneous and cardiac disease. Conclusions: The current evidence supports IFN-I pathway inhibition as a promising approach in SSc. Ongoing trials will help to determine the clinical efficacy, safety, and optimal patient selection for anifrolumab in this rare but severe disease. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Perspectives in Systemic Sclerosis)
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