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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doaj-6c47414193ba4bc98138d87625e5fa3d2021-03-28T23:02:01ZengMDPI AGAntibodies2073-44682021-03-0110121210.3390/antib10020012New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic SclerosisRoberto Lande0Raffaella Palazzo1Anna Mennella2Immacolata Pietraforte3Marius Cadar4Katia Stefanantoni5Curdin Conrad6Valeria Riccieri7Loredana Frasca8Istituto Superiore di Sanita’, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, 00166 Rome, ItalyIstituto Superiore di Sanita’, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, 00166 Rome, ItalyIstituto Superiore di Sanita’, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, 00166 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDipartimento di Scienze Cliniche e Internistiche, Anestesiologiche e Cardiovalscolari, University Sapienza, 00185 Rome, ItalyDipartimento di Scienze Cliniche e Internistiche, Anestesiologiche e Cardiovalscolari, University Sapienza, 00185 Rome, ItalyDepartment of Dermatology, University Hospital CHUV, 1011 Lausanne, SwitzerlandDipartimento di Scienze Cliniche e Internistiche, Anestesiologiche e Cardiovalscolari, University Sapienza, 00185 Rome, ItalyIstituto Superiore di Sanita’, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, 00166 Rome, ItalyChemokine (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.https://www.mdpi.com/2073-4468/10/2/12autoimmune diseaseschemokine (C-X-C motif) ligand 4 (CXCL4)CXCL4-L1autoantibodiesSystemic SclerosisVery Early Diagnosis of Systemic Sclerosis (VEDOSS) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roberto Lande Raffaella Palazzo Anna Mennella Immacolata Pietraforte Marius Cadar Katia Stefanantoni Curdin Conrad Valeria Riccieri Loredana Frasca |
spellingShingle |
Roberto Lande Raffaella Palazzo Anna Mennella Immacolata Pietraforte Marius Cadar Katia Stefanantoni Curdin Conrad Valeria Riccieri Loredana Frasca New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis Antibodies autoimmune diseases chemokine (C-X-C motif) ligand 4 (CXCL4) CXCL4-L1 autoantibodies Systemic Sclerosis Very Early Diagnosis of Systemic Sclerosis (VEDOSS) |
author_facet |
Roberto Lande Raffaella Palazzo Anna Mennella Immacolata Pietraforte Marius Cadar Katia Stefanantoni Curdin Conrad Valeria Riccieri Loredana Frasca |
author_sort |
Roberto Lande |
title |
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_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_sort |
new autoantibody specificities in systemic sclerosis and very early systemic sclerosis |
publisher |
MDPI AG |
series |
Antibodies |
issn |
2073-4468 |
publishDate |
2021-03-01 |
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. |
topic |
autoimmune diseases chemokine (C-X-C motif) ligand 4 (CXCL4) CXCL4-L1 autoantibodies Systemic Sclerosis Very Early Diagnosis of Systemic Sclerosis (VEDOSS) |
url |
https://www.mdpi.com/2073-4468/10/2/12 |
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