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Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders

BACKGROUND: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). AIMS: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications o...

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Autores principales: Bellan, Mattia, Dimagli, Arnaldo, Piccinino, Cristina, Giubertoni, Ailia, Ianniello, Aurora, Grimoldi, Federico, Sguazzotti, Maurizio, Nerviani, Alessandra, Barini, Michela, Carriero, Alessandro, Smirne, Carlo, Burlone, Michela Emma, Rigamonti, Cristina, Minisini, Rosalba, Salmi, Livia, Barbaglia, Matteo Nazzareno, Castello, Luigi Mario, Sola, Daniele, Marino, Paolo, Avanzi, Gian Carlo, Pirisi, Mario, Sainaghi, Pier Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240795/
https://www.ncbi.nlm.nih.gov/pubmed/32454903
http://dx.doi.org/10.1155/2020/2696173
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author Bellan, Mattia
Dimagli, Arnaldo
Piccinino, Cristina
Giubertoni, Ailia
Ianniello, Aurora
Grimoldi, Federico
Sguazzotti, Maurizio
Nerviani, Alessandra
Barini, Michela
Carriero, Alessandro
Smirne, Carlo
Burlone, Michela Emma
Rigamonti, Cristina
Minisini, Rosalba
Salmi, Livia
Barbaglia, Matteo Nazzareno
Castello, Luigi Mario
Sola, Daniele
Marino, Paolo
Avanzi, Gian Carlo
Pirisi, Mario
Sainaghi, Pier Paolo
author_facet Bellan, Mattia
Dimagli, Arnaldo
Piccinino, Cristina
Giubertoni, Ailia
Ianniello, Aurora
Grimoldi, Federico
Sguazzotti, Maurizio
Nerviani, Alessandra
Barini, Michela
Carriero, Alessandro
Smirne, Carlo
Burlone, Michela Emma
Rigamonti, Cristina
Minisini, Rosalba
Salmi, Livia
Barbaglia, Matteo Nazzareno
Castello, Luigi Mario
Sola, Daniele
Marino, Paolo
Avanzi, Gian Carlo
Pirisi, Mario
Sainaghi, Pier Paolo
author_sort Bellan, Mattia
collection PubMed
description BACKGROUND: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). AIMS: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. METHODS: In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. RESULTS: Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K–W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K–W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). CONCLUSIONS: The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.
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spelling pubmed-72407952020-05-23 Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders Bellan, Mattia Dimagli, Arnaldo Piccinino, Cristina Giubertoni, Ailia Ianniello, Aurora Grimoldi, Federico Sguazzotti, Maurizio Nerviani, Alessandra Barini, Michela Carriero, Alessandro Smirne, Carlo Burlone, Michela Emma Rigamonti, Cristina Minisini, Rosalba Salmi, Livia Barbaglia, Matteo Nazzareno Castello, Luigi Mario Sola, Daniele Marino, Paolo Avanzi, Gian Carlo Pirisi, Mario Sainaghi, Pier Paolo Dis Markers Research Article BACKGROUND: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). AIMS: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. METHODS: In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. RESULTS: Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K–W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K–W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). CONCLUSIONS: The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations. Hindawi 2020-05-12 /pmc/articles/PMC7240795/ /pubmed/32454903 http://dx.doi.org/10.1155/2020/2696173 Text en Copyright © 2020 Mattia Bellan et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bellan, Mattia
Dimagli, Arnaldo
Piccinino, Cristina
Giubertoni, Ailia
Ianniello, Aurora
Grimoldi, Federico
Sguazzotti, Maurizio
Nerviani, Alessandra
Barini, Michela
Carriero, Alessandro
Smirne, Carlo
Burlone, Michela Emma
Rigamonti, Cristina
Minisini, Rosalba
Salmi, Livia
Barbaglia, Matteo Nazzareno
Castello, Luigi Mario
Sola, Daniele
Marino, Paolo
Avanzi, Gian Carlo
Pirisi, Mario
Sainaghi, Pier Paolo
Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title_full Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title_fullStr Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title_full_unstemmed Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title_short Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders
title_sort role of gas6 and tam receptors in the identification of cardiopulmonary involvement in systemic sclerosis and scleroderma spectrum disorders
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240795/
https://www.ncbi.nlm.nih.gov/pubmed/32454903
http://dx.doi.org/10.1155/2020/2696173
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