Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment

Systemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud’s phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of prev...

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Main Authors: Eloisa Romano, Irene Rosa, Bianca Saveria Fioretto, Marco Matucci-Cerinic, Mirko Manetti
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/12/11/1790
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author Eloisa Romano
Irene Rosa
Bianca Saveria Fioretto
Marco Matucci-Cerinic
Mirko Manetti
author_facet Eloisa Romano
Irene Rosa
Bianca Saveria Fioretto
Marco Matucci-Cerinic
Mirko Manetti
author_sort Eloisa Romano
collection DOAJ
description Systemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud’s phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of previously described associations between the circulating levels of soluble junctional adhesion molecules (sJAMs) and SSc clinical features, here, we measured sJAM-A and sJAM-C levels by enzyme-linked immunosorbent assay in serum samples from a large case series of 110 SSc patients and 85 healthy controls, focusing on their possible association with peripheral vascular clinical features and their potential as biomarkers that are either diagnostic or mirror SSc-related microvasculopathy severity. Our data demonstrated that serum sJAM-A and sJAM-C are significantly increased in patients with SSc vs. healthy controls, especially in those featuring early/active NVC patterns and the presence of ischemic DUs. Moreover, circulating sJAM-C levels showed good diagnostic accuracy in discriminating between patients and controls, as assessed by receiver operator characteristics curve analysis. Finally, logistic regression revealed that, when comparing sJAM-A to sJAM-C, the latter might be better suited as a biomarker for SSc-related DUs. Our promising findings provide the necessary groundwork for longitudinal follow-up analyses of SSc patients aiming to assess whether circulating sJAM-C levels might be predictive for the development of new DUs, as well as DU recurrence and/or refractoriness to targeted therapies.
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spelling doaj.art-0ecf499dc822464e88144cc861af95422023-11-24T05:30:58ZengMDPI AGLife2075-17292022-11-011211179010.3390/life12111790Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular ImpairmentEloisa Romano0Irene Rosa1Bianca Saveria Fioretto2Marco Matucci-Cerinic3Mirko Manetti4Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySystemic sclerosis (SSc, scleroderma) is a severe disease characterized by peripheral microcirculation abnormalities manifesting with Raynaud’s phenomenon, nailfold videocapillaroscopic (NVC) changes, and even ischemic digital ulcers (DUs) that are often refractory to treatments. In the wake of previously described associations between the circulating levels of soluble junctional adhesion molecules (sJAMs) and SSc clinical features, here, we measured sJAM-A and sJAM-C levels by enzyme-linked immunosorbent assay in serum samples from a large case series of 110 SSc patients and 85 healthy controls, focusing on their possible association with peripheral vascular clinical features and their potential as biomarkers that are either diagnostic or mirror SSc-related microvasculopathy severity. Our data demonstrated that serum sJAM-A and sJAM-C are significantly increased in patients with SSc vs. healthy controls, especially in those featuring early/active NVC patterns and the presence of ischemic DUs. Moreover, circulating sJAM-C levels showed good diagnostic accuracy in discriminating between patients and controls, as assessed by receiver operator characteristics curve analysis. Finally, logistic regression revealed that, when comparing sJAM-A to sJAM-C, the latter might be better suited as a biomarker for SSc-related DUs. Our promising findings provide the necessary groundwork for longitudinal follow-up analyses of SSc patients aiming to assess whether circulating sJAM-C levels might be predictive for the development of new DUs, as well as DU recurrence and/or refractoriness to targeted therapies.https://www.mdpi.com/2075-1729/12/11/1790systemic sclerosissclerodermajunctional adhesion moleculessJAM-AsJAM-Cperipheral microvascular damage
spellingShingle Eloisa Romano
Irene Rosa
Bianca Saveria Fioretto
Marco Matucci-Cerinic
Mirko Manetti
Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
Life
systemic sclerosis
scleroderma
junctional adhesion molecules
sJAM-A
sJAM-C
peripheral microvascular damage
title Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
title_full Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
title_fullStr Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
title_full_unstemmed Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
title_short Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment
title_sort increased circulating soluble junctional adhesion molecules in systemic sclerosis association with peripheral microvascular impairment
topic systemic sclerosis
scleroderma
junctional adhesion molecules
sJAM-A
sJAM-C
peripheral microvascular damage
url https://www.mdpi.com/2075-1729/12/11/1790
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