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Article ; Online: New lessons for an old problem: ASSET open-label extension.

Del Galdo, Francesco

The Lancet. Rheumatology

2020 Volume 2, Issue 12, Page(s) e726–e727

Language	English
Publishing date	2020-10-19
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(20)30379-9
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Article ; Online: More to B: the growing evidence to inform targeting B cells in scleroderma.

Bosello, Silvia Laura / Vital, Edward M / Del Galdo, Francesco

Rheumatology (Oxford, England)

2023 Volume 62, Issue 5, Page(s) 1730–1732

MeSH term(s)	Humans ; B-Lymphocytes ; Scleroderma, Localized ; Scleroderma, Systemic
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac677
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article ; Online: Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives.

De Lorenzis, Enrico / Wasson, Christopher William / Del Galdo, Francesco

Journal of scleroderma and related disorders

2023 Volume 9, Issue 1, Page(s) 7–15

Abstract: The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can ... ...

Abstract	The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.
Language	English
Publishing date	2023-06-20
Publishing country	England
Document type	Journal Article ; Review
ISSN	2397-1991
ISSN (online)	2397-1991
DOI	10.1177/23971983231181727
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Article ; Online: Systemic sclerosis interstitial lung disease: unmet needs and potential solutions.

Liakouli, Vasiliki / Ciancio, Antonio / Del Galdo, Francesco / Giacomelli, Roberto / Ciccia, Francesco

Nature reviews. Rheumatology

2023 Volume 20, Issue 1, Page(s) 21–32

Abstract: Systemic sclerosis (SSc), or scleroderma, is a rare, complex, systemic autoimmune disease of unknown aetiology, characterized by high morbidity and mortality often resulting from cardiopulmonary complications such as interstitial lung disease and ... ...

Abstract	Systemic sclerosis (SSc), or scleroderma, is a rare, complex, systemic autoimmune disease of unknown aetiology, characterized by high morbidity and mortality often resulting from cardiopulmonary complications such as interstitial lung disease and pulmonary arterial hypertension. Despite substantial progress in unravelling the pathways involved in the pathogenesis of SSc and the increasing number of therapeutic targets tested in clinical trials, there is still no cure for this disease, although several proposed treatments might limit the involvement of specific organs, thereby slowing the natural history of the disease. A specific focus of recent research has been to address the plethora of unmet needs regarding the global management of SSc-related interstitial lung disease, including its pathogenesis, early diagnosis, risk stratification of patients, appropriate treatment regimens and monitoring of treatment response, as well as the definition of progression and predictors of progression and mortality. More refined stratification of patients on the basis of clinical features, molecular signatures, identification of subpopulations with distinct clinical trajectories and implementation of outcome measures for future clinical trials could also improve therapeutic management strategies, helping to avoid poor outcomes related to lung involvement.
MeSH term(s)	Humans ; Lung Diseases, Interstitial/etiology ; Lung Diseases, Interstitial/therapy ; Lung Diseases, Interstitial/diagnosis ; Scleroderma, Systemic/diagnosis ; Scleroderma, Systemic/therapy ; Scleroderma, Systemic/complications ; Lung
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-023-01044-x
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Zs.A 6338: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article: Biomarkers as an opportunity to stratify for outcome in systemic sclerosis.

Abignano, Giuseppina / Del Galdo, Francesco

European journal of rheumatology

2020 Volume 7, Issue Suppl 3, Page(s) S193–S202

Abstract: Systemic sclerosis (SSc) is a highly complex disease whose heterogeneity includes multiple aspects of the condition, such as clinical presentation, progression, extent and type of organ involvement, and clinical outcomes. Thus far, these features remain ... ...

Abstract	Systemic sclerosis (SSc) is a highly complex disease whose heterogeneity includes multiple aspects of the condition, such as clinical presentation, progression, extent and type of organ involvement, and clinical outcomes. Thus far, these features remain not easily predictable both at the patient group level and in a given patient with regard to age at onset and clinical course. The unpredictable clinical course represents an obstacle to focusing potentially effective treatment in patients that need it the most. At the time of organ involvement and clinical diagnosis, most of the clinical manifestations are irreversible; therefore, predicting outcomes becomes crucial. This can explain the multiple attempts to identify prognostic, predictive, and monitoring-both soluble and imaging-biomarkers over the past years. They range from the currently most used biomarkers, the autoantibodies associated with disease-specific clinical features and course, to the single recently proposed skin, lung, cardiac involvement biomarkers and to the composite scores capturing multiple aspects of the disease. This review will focus on soluble and imaging biomarkers that recently showed promising evidence for outcome stratification in patients with SSc.
Language	English
Publishing date	2020-07-20
Publishing country	Turkey
Document type	Journal Article ; Review
ZDB-ID	2873727-1
ISSN	2148-4279 ; 2147-9720
ISSN (online)	2148-4279
ISSN	2147-9720
DOI	10.5152/eurjrheum.2020.19065
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Article: A special European Journal of Rheumatology issue on systemic sclerosis: What and why?

Del Galdo, Francesco / Matucci-Cerinic, Marco

European journal of rheumatology

2020 Volume 7, Issue Suppl 3, Page(s) S137–S138

Language	English
Publishing date	2020-10-01
Publishing country	Turkey
Document type	Editorial
ZDB-ID	2873727-1
ISSN	2148-4279 ; 2147-9720
ISSN (online)	2148-4279
ISSN	2147-9720
DOI	10.5152/eurjrheum.2020.090121
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Article ; Online: Serum CCL24 as a biomarker of fibrotic and vascular disease severity in Systemic Sclerosis.

De Lorenzis, Enrico / Mor, Adi / Ross, Rebecca L / Di Donato, Stefano / Aricha, Revital / Vaknin, Ilan / Del Galdo, Francesco

Arthritis care & research

2024

Abstract: Background: Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. The C-C Motif Chemokine Ligand 24 (CCL24 or Eotaxin2) has been shown to promote ... ...

Abstract	Background: Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. The C-C Motif Chemokine Ligand 24 (CCL24 or Eotaxin2) has been shown to promote microangiopathic, pro-inflammatory, and pro-fibrotic processes in preclinical models of SSc. Here we study serum CCL24 levels in a real-life cohort of SSc patients, to determine its distribution across disease features and its value in predicting disease progression and related mortality. Methods: Serum CCL24 was assessed in an observational cohort of consecutively enrolled SSc patients. A high CCL24 cut-off was defined based on its distribution in a matched cohort of healthy controls. Disease progression and mortality were analysed from the date of serum assessment. Results: Two-hundred-thirteen consecutively enrolled patients with SSc were included in this analysis. Median disease duration was 6 years (IQR 3-14), 28.6% of patients presented with interstitial lung disease (ILD), 46.9% had digital ulcers and 25.3% showed high CCL24 serum concentration. High CCL24 patients were more frequently male, with anti-SCL-70 positive, with a diagnosis of ILD and synovitis (p<0.05 for all). Notably, high CCL24 patients had lower DLco and higher prevalence of digital ulcers, telangiectasias, and calcinosis (p<0.05 for all). In a longitudinal setting, high CCL24 was associated with greater lung function decline and with higher disease-related mortality. Conclusion: Serum CCL24 is a biomarker of disease severity across fibrotic and vascular disease manifestations. These data support the development of therapies targeting CCL24 as a novel comprehensive therapeutic target in SSc.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.25344
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Zs.A 2446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 24: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis.

Ross, Rebecca L / Mavria, Georgia / Del Galdo, Francesco / Elies, Jacobo

Frontiers in physiology

2022 Volume 13, Page(s) 900631

Abstract: Systemic sclerosis (SSc) is a terminal disease characterized by vasculopathy, tissue fibrosis, and autoimmunity. Although the exact etiology of SSc remains unknown, endothelial dysfunction, oxidative stress, and calcium handling dysregulation have been ... ...

Abstract	Systemic sclerosis (SSc) is a terminal disease characterized by vasculopathy, tissue fibrosis, and autoimmunity. Although the exact etiology of SSc remains unknown, endothelial dysfunction, oxidative stress, and calcium handling dysregulation have been associated with a large number of SSc-related complications such as neointima formation, vasculogenesis, pulmonary arterial hypertension, impaired angiogenesis, and cardiac arrhythmias. Hemeoxygenase-1 (HO-1) is an antioxidant enzyme involved in multiple biological actions in the cardiovascular system including vascular tone, angiogenesis, cellular proliferation, apoptosis, and oxidative stress. The aim of this work was to investigate the physiological role of HO-1 and its relevance in the cardiovascular complications occurring in SSc. We found that, in early phases of SSc, the expression of HO-1 in dermal fibroblast is lower compared to those isolated from healthy control individuals. This is particularly relevant as reduction of the HO-1/CO signaling pathway is associated with endothelial dysfunction and vasculopathy. We show evidence of the role of HO-1/carbon monoxide (CO) signaling pathway in calcium handling. Using an
Language	English
Publishing date	2022-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.900631
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Article ; Online: Autonomic dysfunction in systemic sclerosis: A scoping review.

Di Battista, Marco / Wasson, Christopher W / Alcacer-Pitarch, Begonya / Del Galdo, Francesco

Seminars in arthritis and rheumatism

2023 Volume 63, Page(s) 152268

Abstract: Introduction: Over the years several lines of evidence have implied a pathological involvement of autonomic nervous system (ANS) in systemic sclerosis (SSc). However, the relationship between autonomic dysfunction and SSc is not yet fully understood. ... ...

Abstract	Introduction: Over the years several lines of evidence have implied a pathological involvement of autonomic nervous system (ANS) in systemic sclerosis (SSc). However, the relationship between autonomic dysfunction and SSc is not yet fully understood. The aims of this scoping review were to map the research done in this field and inform future research to investigate pathogenic hypotheses of ANS involvement. Methods: We performed a scoping review of publications collected through a literature search of MEDLINE and Web of Science databases, looking for dysautonomia in SSc. We included original data from papers that addressed ANS involvement in SSc regarding pathogenesis, clinical presentation and diagnostic tools. Results: 467 papers were identified, 109 studies were selected to be included in the present review, reporting data from a total of 2742 SSc patients. Cardiovascular system was the most extensively investigated, assessing heart rate variability with 24 h HolterECG or Ewing's autonomic tests. Important signs of dysautonomia were also found in digital vasculopathy, gastrointestinal system and SSc skin, assessed both with non-invasive techniques and histologically. Research hypotheses mainly regarding the relationship between sympathetic system - ischemia and the role of neurotrophins were then developed and discussed. Conclusion: We described the currently available evidence on pathogenesis, clinical presentation and diagnostic assessment of dysautonomia in SSc patients. A strong influence of ANS deregulation on SSc clearly emerges from the literature. Future research is warranted to clarify the mechanisms and timing of autonomic dysfunction in SSc.
MeSH term(s)	Humans ; Autonomic Nervous System Diseases/etiology ; Autonomic Nervous System ; Heart Rate/physiology ; Scleroderma, Systemic/complications ; Gastrointestinal Tract
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2023.152268
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Zs.A 790: Show issues

Location:
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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Circulating extracellular vesicles in the context of interstitial lung disease related to systemic sclerosis: A scoping literature review.

De Lorenzis, Enrico / Rindone, Andrea / Di Donato, Stefano / Del Galdo, Francesco

Autoimmunity reviews

2023 Volume 22, Issue 9, Page(s) 103401

Abstract: Background: Interstitial lung disease (ILD) is a significant cause of disability and mortality in systemic sclerosis (SSc), where lung fibrosis stems from the interaction of cells within the epithelial, endothelial, interstitial, and immune cell ... ...

Abstract	Background: Interstitial lung disease (ILD) is a significant cause of disability and mortality in systemic sclerosis (SSc), where lung fibrosis stems from the interaction of cells within the epithelial, endothelial, interstitial, and immune cell compartments. Extracellular vesicles (EVs) are particles released by cells capable of transferring functionally active molecules, playing a crucial role in intercellular communication. This scoping review aims to identify and map existing evidence about the role of EVs as biomarkers or pathophysiological actors in SSc-ILD. It also retrospectively assesses the compliance of published articles with the current reporting guidelines established by the International Society of Extracellular Vesicles (ISEV). Methods: This scoping review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The searches were conducted up until 31 May 2023, with no restrictions on the starting year. Results: Out of 778 publications identified and screened, 9 references were selected. The eligible studies collectively involved a total of 539 SSc patients, with 220 patients presenting with ILD, as demonstrated by high-resolution computed tomography. The studies largely focused on the quantitative assessment of EVs through flow cytometry, primarily concerning larger EVs. The studies primarily focused on the association of EV features with vascular complications, with fibrotic pulmonary involvement typically explored as a secondary finding. The evaluated patients' clinical characteristics were significantly heterogeneous across the studies as well as the association of EV features with the evidence of ILD but none of them longitudinally investigated the relationships with SSc-ILD prognosis. Adherence of these exploratory studies to ISEV reporting guidelines in terms of EV nomenclature, reporting of pre-analytic variables, and qualitative verification of EV separation products was incomplete. Conclusions: The evidence concerning the clinical association of EV features is limited and conflicting. The interpretation of available data is substantially biased due to patient selection tailored for vascular complications, heterogeneity of separation methodology, and a lack of validation procedures.
MeSH term(s)	Humans ; Retrospective Studies ; Lung Diseases, Interstitial/complications ; Scleroderma, Systemic/complications ; Pulmonary Fibrosis/complications ; Extracellular Vesicles ; Lung
Language	English
Publishing date	2023-07-22
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2023.103401
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Zs.A 5913: Show issues

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