ArticleInternational journal of molecular sciences2020
Anti-CXCL4 Antibody Reactivity Is Present in Systemic Sclerosis (SSc) and Correlates with the SSc Type I Interferon Signature.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Tetrameric assembly disruption impairs CXCL4 chaperon ability for DNA and type I interferon immune amplification.Communications biology · 2026Article
- CAR-T cells in systemic sclerosis.Clinical rheumatology · 2026Review
- Anifrolumab-A Potential New Systemic Sclerosis Treatment.Journal of clinical medicine · 2026Review
- Emerging Cell-Based Therapies for Systemic Sclerosis: From Stem Cells to CAR-T Cells.Current issues in molecular biology · 2026Review
- PF4 Autoantibody Complexes Cause Activation of Integrins αIIbβ3 and αvβ3 and Possible Subsequent Thrombosis and Autoimmune Diseases.International journal of molecular sciences · 2025Article
- Article
- Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences.Clinical reviews in allergy & immunology · 2025Review
- A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis.Gels (Basel, Switzerland) · 2025Article
- Undifferentiated connective tissue disease: the diagnoses critically revised-experience of a single center.Clinical and experimental medicine · 2025Article
- Undifferentiated connective tissue disease: the diagnoses critically revised-experience of a single center.Clinical and experimental medicine · 2025Article
- The Role of CXCL4 in Systemic Sclerosis: DAMP, Auto-Antigen and Biomarker.International journal of molecular sciences · 2025Review
- Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes.Arthritis research & therapy · 2025Article
- The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies.Clinical and experimental immunology · 2025Review
- Serglycin controls megakaryocyte retention of platelet factor 4 and influences megakaryocyte fate in bone marrow.Blood advances · 2025Article
- CXCL4 deficiency limits M4 macrophage infiltration and attenuates hyperoxia-induced lung injury.Molecular medicine (Cambridge, Mass.) · 2024Article
- Plasma CXCL4-DNA/RNA Complexes and Anti-CXCL4 Antibodies Modulation in an SSc Cohort under Iloprost Treatment.Reports (MDPI) · 2024Article
- Type I Interferons in Systemic Autoimmune Rheumatic Diseases: Pathogenesis, Clinical Features and Treatment Options.Mediterranean journal of rheumatology · 2024Review
- New, Old, and Shared Antibody Specificities in Autoimmune Diseases.Antibodies (Basel, Switzerland) · 2024Article
- Role of platelet factor 4 in arteriovenous fistula maturation failure: What do we know so far?The journal of vascular access · 2024Review
- Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Systemic sclerosis (SSc) is characterized by skin/internal organ fibrosis, vasculopathy and autoimmunity. Chemokine (C-X-C motif) ligand 4 (CXCL4) is an SSc biomarker, predicting unfavorable prognosis and lung fibrosis. CXCL4 binds DNA/RNA and favors interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs), contributing to the type I IFN (IFN-I) signature in SSc patients. However, whether CXCL4 is an autoantigen in SSc is unknown. Here, we show that at least half of SSc patients show consistent antibody reactivity to CXCL4. T-cell proliferation to CXCL4, tested in a limited number of patients, correlates with anti-CXCL4 antibody reactivity. Antibodies to CXCL4 mostly correlate with circulating IFN-α levels and are significantly higher in patients with lung fibrosis in two independent SSc cohorts. Antibodies to CXCL4 implement the CXCL4-DNA complex's effect on IFN-α production by pDCs; CXCL4-DNA/RNA complexes stimulate purified human B-cells to become antibody-secreting plasma cells in vitro. These data indicate that CXCL4 is indeed an autoantigen in SSc and suggest that CXCL4, and CXCL4-specific autoantibodies, can fuel a harmful loop: CXCL4-DNA/RNA complexes induce IFN-α in pDCs and direct B-cell stimulation, including the secretion of anti-CXCL4 antibodies. Anti-CXCL4 antibodies may further increase pDC stimulation and IFN-α release in vivo, creating a vicious cycle which sustains the SSc IFN-I signature and general inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.