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Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers

Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the stro...

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Autores principales: Cavazzana, Ilaria, Vojinovic, Tamara, Airo’, Paolo, Fredi, Micaela, Ceribelli, Angela, Pedretti, Eleonora, Lazzaroni, Maria Grazia, Garrafa, Emirena, Franceschini, Franco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167150/
https://www.ncbi.nlm.nih.gov/pubmed/35716254
http://dx.doi.org/10.1007/s12016-022-08946-w
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author Cavazzana, Ilaria
Vojinovic, Tamara
Airo’, Paolo
Fredi, Micaela
Ceribelli, Angela
Pedretti, Eleonora
Lazzaroni, Maria Grazia
Garrafa, Emirena
Franceschini, Franco
author_facet Cavazzana, Ilaria
Vojinovic, Tamara
Airo’, Paolo
Fredi, Micaela
Ceribelli, Angela
Pedretti, Eleonora
Lazzaroni, Maria Grazia
Garrafa, Emirena
Franceschini, Franco
author_sort Cavazzana, Ilaria
collection PubMed
description Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of “seronegative” SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2–7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients’ stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns’ interpretation. The gold-standard technique for autoantibodies’ identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients.
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spelling pubmed-101671502023-05-10 Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers Cavazzana, Ilaria Vojinovic, Tamara Airo’, Paolo Fredi, Micaela Ceribelli, Angela Pedretti, Eleonora Lazzaroni, Maria Grazia Garrafa, Emirena Franceschini, Franco Clin Rev Allergy Immunol Article Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad’s phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of “seronegative” SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2–7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients’ stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns’ interpretation. The gold-standard technique for autoantibodies’ identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients. Springer US 2022-06-18 2023 /pmc/articles/PMC10167150/ /pubmed/35716254 http://dx.doi.org/10.1007/s12016-022-08946-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cavazzana, Ilaria
Vojinovic, Tamara
Airo’, Paolo
Fredi, Micaela
Ceribelli, Angela
Pedretti, Eleonora
Lazzaroni, Maria Grazia
Garrafa, Emirena
Franceschini, Franco
Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title_full Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title_fullStr Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title_full_unstemmed Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title_short Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers
title_sort systemic sclerosis-specific antibodies: novel and classical biomarkers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167150/
https://www.ncbi.nlm.nih.gov/pubmed/35716254
http://dx.doi.org/10.1007/s12016-022-08946-w
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