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New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis

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...

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Autores principales: Lande, Roberto, Palazzo, Raffaella, Mennella, Anna, Pietraforte, Immacolata, Cadar, Marius, Stefanantoni, Katia, Conrad, Curdin, Riccieri, Valeria, Frasca, Loredana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103273/
https://www.ncbi.nlm.nih.gov/pubmed/33800661
http://dx.doi.org/10.3390/antib10020012
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author Lande, Roberto
Palazzo, Raffaella
Mennella, Anna
Pietraforte, Immacolata
Cadar, Marius
Stefanantoni, Katia
Conrad, Curdin
Riccieri, Valeria
Frasca, Loredana
author_facet Lande, Roberto
Palazzo, Raffaella
Mennella, Anna
Pietraforte, Immacolata
Cadar, Marius
Stefanantoni, Katia
Conrad, Curdin
Riccieri, Valeria
Frasca, Loredana
author_sort Lande, Roberto
collection PubMed
description 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.
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spelling pubmed-81032732021-05-08 New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis Lande, Roberto Palazzo, Raffaella Mennella, Anna Pietraforte, Immacolata Cadar, Marius Stefanantoni, Katia Conrad, Curdin Riccieri, Valeria Frasca, Loredana Antibodies (Basel) Article 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. MDPI 2021-03-28 /pmc/articles/PMC8103273/ /pubmed/33800661 http://dx.doi.org/10.3390/antib10020012 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Lande, Roberto
Palazzo, Raffaella
Mennella, Anna
Pietraforte, Immacolata
Cadar, Marius
Stefanantoni, Katia
Conrad, Curdin
Riccieri, Valeria
Frasca, Loredana
New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title_full New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title_fullStr New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title_full_unstemmed New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title_short New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis
title_sort new autoantibody specificities in systemic sclerosis and very early systemic sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103273/
https://www.ncbi.nlm.nih.gov/pubmed/33800661
http://dx.doi.org/10.3390/antib10020012
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