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New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis

Authors :
Roberto Lande
Raffaella Palazzo
Anna Mennella
Immacolata Pietraforte
Marius Cadar
Katia Stefanantoni
Curdin Conrad
Valeria Riccieri
Loredana Frasca
Source :
Antibodies, Vol 10, Iss 2, p 12 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Chemokine (C-X-C motif) ligand 4 (CXCL4) is a biomarker of unfavorable prognosis in Systemic Sclerosis (SSc), a potentially severe autoimmune condition, characterized by vasculitis, fibrosis and interferon (IFN)-I-signature. We recently reported that autoantibodies to CXCL4 circulate in SSc patients and correlate with IFN-α. Here, we used shorter versions of CXCL4 and CXCL4-L1, the CXCL4 non-allelic variant, to search for autoantibodies exclusively reacting to one or the other CXCL4 form. Moreover, to address whether anti-CXCL4/CXCL4-L1 antibodies were present before SSc onset and predicted SSc-progression, we longitudinally studied two VEDOSS (Very Early Diagnosis of Systemic Sclerosis) patient cohorts, separating SSc-progressors from SSc-non-progressors. We found that anti-CXCL4-specific autoantibodies were present in both SSc and VEDOSS patients (both SSc-progressors and SSc-non-progressors). Anti-CXCL4-L1-specific autoantibodies were especially detected in long-standing SSc (lsSSc). Anti-CXCL4/CXCL4-L1 antibodies correlated with IFN-α and with specific SSc-skin features but only in lsSSc and not in early SSc (eaSSc) or VEDOSS. Thus, a broader antibody response, with reactivity spreading to CXCL4-L1, is characteristic of lsSSc. The early anti-CXCL4 autoantibody response seems qualitatively different from, and likely less pathogenic than, that observed in advanced SSc. Lastly, we confirm that anti-CXCL4 autoantibodies are SSc-biomarkers and uncover that also CXCL4-L1 becomes an autoantigen in lsSSc.

Details

Language :
English
ISSN :
10020012 and 20734468
Volume :
10
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Antibodies
Publication Type :
Academic Journal
Accession number :
edsdoj.6c47414193ba4bc98138d87625e5fa3d
Document Type :
article
Full Text :
https://doi.org/10.3390/antib10020012