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Article

New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis

1
Istituto Superiore di Sanita’, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, 00166 Rome, Italy
2
Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland
3
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
4
Dipartimento di Scienze Cliniche e Internistiche, Anestesiologiche e Cardiovalscolari, University Sapienza, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Daniel Hawiger
Antibodies 2021, 10(2), 12; https://doi.org/10.3390/antib10020012
Received: 20 January 2021 / Revised: 16 February 2021 / Accepted: 11 March 2021 / Published: 28 March 2021
(This article belongs to the Special Issue New, Old, and Shared Antibody Specificities in Autoimmune Diseases)
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. View Full-Text
Keywords: autoimmune diseases; chemokine (C-X-C motif) ligand 4 (CXCL4); CXCL4-L1; autoantibodies; Systemic Sclerosis; Very Early Diagnosis of Systemic Sclerosis (VEDOSS); IFN-I signature; biomarkers autoimmune diseases; chemokine (C-X-C motif) ligand 4 (CXCL4); CXCL4-L1; autoantibodies; Systemic Sclerosis; Very Early Diagnosis of Systemic Sclerosis (VEDOSS); IFN-I signature; biomarkers
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MDPI and ACS Style

Lande, R.; Palazzo, R.; Mennella, A.; Pietraforte, I.; Cadar, M.; Stefanantoni, K.; Conrad, C.; Riccieri, V.; Frasca, L. New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis. Antibodies 2021, 10, 12. https://doi.org/10.3390/antib10020012

AMA Style

Lande R, Palazzo R, Mennella A, Pietraforte I, Cadar M, Stefanantoni K, Conrad C, Riccieri V, Frasca L. New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis. Antibodies. 2021; 10(2):12. https://doi.org/10.3390/antib10020012

Chicago/Turabian Style

Lande, Roberto, Raffaella Palazzo, Anna Mennella, Immacolata Pietraforte, Marius Cadar, Katia Stefanantoni, Curdin Conrad, Valeria Riccieri, and Loredana Frasca. 2021. "New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis" Antibodies 10, no. 2: 12. https://doi.org/10.3390/antib10020012

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