Titre
Anti-CXCL4 Antibody Reactivity Is Present in Systemic Sclerosis (SSc) and Correlates with the SSc Type I Interferon Signature.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Lande, R.
Auteure/Auteur
Mennella, A.
Auteure/Auteur
Palazzo, R.
Auteure/Auteur
Pietraforte, I.
Auteure/Auteur
Stefanantoni, K.
Auteure/Auteur
Iannace, N.
Auteure/Auteur
Butera, A.
Auteure/Auteur
Boirivant, M.
Auteure/Auteur
Pica, R.
Auteure/Auteur
Conrad, C.
Auteure/Auteur
Chizzolini, C.
Auteure/Auteur
Riccieri, V.
Auteure/Auteur
Frasca, L.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1422-0067
Statut éditorial
Publié
Date de publication
2020-07-19
Volume
21
Numéro
14
Première page
5102
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
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.
Sujets
PID Serval
serval:BIB_565271192042
PMID
Open Access
Oui
Date de création
2020-08-11T09:41:59.615Z
Date de création dans IRIS
2025-05-20T17:35:40Z
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Nom
Anti-CXCL4 Antibody Reactivity Is Present in.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.97 MB
Format
Adobe PDF
PID Serval
serval:BIB_565271192042.P001
Somme de contrôle
(MD5):10bdd95a1f48bd5b7af65e358bfda109