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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8103273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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