Increased malignancies in systemic sclerosis

Vondenberg, Jaime A; Muruganandam, Maheswari; Nunez, Sharon E; Emil, N. Suzanne; Sibbitt, Wilmer L.

doi:10.1111/1756-185x.14244

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…Supporting this evidence is the response of some SSc patients to B-cell-targeted therapies and the role of activated B cells in the success of allogeneic bone marrow transplantation for the treatment of SSc [24,25,[55][56][57][58][59][60]. In addition, SSc patients have macro-and microvascular damage and impaired peripheral blood perfusion [6,[48][49][50][51][52][53].…”

Section: Introductionmentioning

confidence: 96%

“…It is unusual to find two different SSc-specific autoantibodies simultaneously in the same individual [29][30][31][32][33][48][49][50][51][52][53][54][55][92][93][94][95][96][97][98][99]. Mortality in SSc patients is significantly increased and usually related to the life-threatening manifestations of SSc, including PAH, ILD, SRC, cardiac involvement, tumors, and infections, which are also related to immunosuppressive drugs [8,9,34,48,[56][57][58][100][101][102][103][104][105][106][107][108][109].…”

Section: Introductionmentioning

confidence: 99%

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Biomarkers in Systemic Sclerosis: An Overview

Di Maggio,

Confalonieri,

Salton

et al. 2023

CIMB

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Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor β (TGF-β) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Biomarkers in Systemic Sclerosis: An Overview

Di Maggio,

Confalonieri,

Salton

et al. 2023

CIMB

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“…Notably, the 5-year survival rate for SSc patients is reported to be 74.9%, which significantly declines to 40% in cases where visceral organ damage occurs (4,5). Moreover, the incidence of malignancy was significantly increased in SSc patients (6). Therefore, SSc imposes a substantial financial burden on patients and their families (7,8).…”

Section: Introductionmentioning

confidence: 99%

Tree shrews as a new animal model for systemic sclerosis research

Zheng,

Chen,

et al. 2024

Front. Immunol.

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ObjectiveSystemic sclerosis (SSc) is a chronic systemic disease characterized by immune dysregulation and fibrosis for which there is no effective treatment. Animal models are crucial for advancing SSc research. Tree shrews are genetically, anatomically, and immunologically closer to humans than rodents. Thus, the tree shrew model provides a unique opportunity for translational research in SSc.MethodsIn this study, a SSc tree shrew model was constructed by subcutaneous injection of different doses of bleomycin (BLM) for 21 days. We assessed the degree of inflammation and fibrosis in the skin and internal organs, and antibodies in serum. Furthermore, RNA sequencing and a series of bioinformatics analyses were performed to analyze the transcriptome changes, hub genes and immune infiltration in the skin tissues of BLM induced SSc tree shrew models. Multiple sequence alignment was utilized to analyze the conservation of selected target genes across multiple species.ResultsSubcutaneous injection of BLM successfully induced a SSc model in tree shrew. This model exhibited inflammation and fibrosis in skin and lung, and some developed esophageal fibrosis and secrum autoantibodies including antinuclear antibodies and anti-scleroderma-70 antibody. Using RNA sequencing, we compiled skin transcriptome profiles in SSc tree shrew models. 90 differentially expressed genes (DEGs) were identified, which were mainly enriched in the PPAR signaling pathway, tyrosine metabolic pathway, p53 signaling pathway, ECM receptor interaction and glutathione metabolism, all of which are closely associated with SSc. Immune infiltration analysis identified 20 different types of immune cells infiltrating the skin of the BLM-induced SSc tree shrew models and correlations between those immune cells. By constructing a protein-protein interaction (PPI) network, we identified 10 hub genes that were significantly highly expressed in the skin of the SSc models compared to controls. Furthermore, these genes were confirmed to be highly conserved in tree shrews, humans and mice.ConclusionThis study for the first time comfirmed that tree shrew model of SSc can be used as a novel and promising experimental animal model to study the pathogenesis and translational research in SSc.

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“… 21 Anti-topoisomerase I antibodies also predict the development of diffuse cutaneous involvement with SSc and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD) ( Figure 2 ). 21 , 23 …”

Section: Introductionmentioning

confidence: 99%

“…21 Antitopoisomerase I antibodies also predict the development of diffuse cutaneous involvement with SSc and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD) (Figure 2). 21,23 Mortality in SSc is significantly increased and usually related to life-threatening manifestations of SSc including interstitial lung disease, scleroderma renal crisis, pulmonary arterial hypertension, cardiac involvement, secondary malignancy, and infections from tissue necrosis, aspiration pneumonia, and immunosuppression. 1,24…”

Section: Introductionmentioning

confidence: 99%

Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis

Muruganandam,

Ariza-Hutchinson,

Patel

et al. 2023

JIR

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Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, vasoinstability, and decreased perfusion with ischemia, inflammation, and exuberant fibrosis of the skin and internal organs. Biomarkers are analytic indicators of the biological and disease processes within an individual that can be accurately and reproducibly measured. The field of biomarkers in SSc is complex as recent studies have implicated at least 240 pathways and dysregulated proteins in SSc pathogenesis. Anti-nuclear antibodies (ANA) are classical biomarkers with well-described clinical classifications and are present in more than 90% of SSc patients and include anti-centromere, anti-Th/To, anti-RNA polymerase III, and anti-topoisomerase I antibodies. Transforming growth factor-β (TGF-β) is central to the fibrotic process of SSc and is intimately intertwined with other biomarkers. Tyrosine kinases, interferon-1 signaling, IL-6 signaling, endogenous thrombin, peroxisome proliferator-activated receptors (PPARs), lysophosphatidic acid receptors, and amino acid metabolites are new biomarkers with the potential for developing new therapeutic agents. Other biomarkers implicated in SSc-ILD include signal transducer and activator of transcription 4 (STAT4), CD226 (DNAX accessory molecule 1), interferon regulatory factor 5 (IRF5), interleukin-1 receptor–associated kinase-1 (IRAK1), connective tissue growth factor (CTGF), pyrin domain containing 1 (NLRP1), T-cell surface glycoprotein zeta chain (CD3ζ) or CD247, the NLR family, SP-D (surfactant protein), KL-6, leucine-rich α2-glycoprotein-1 (LRG1), CCL19, genetic factors including DRB1 alleles, the interleukins (IL-1, IL-4, IL-6, IL-8, IL-10 IL-13, IL-16, IL-17, IL-18, IL-22, IL-32, and IL-35), the chemokines CCL (2,3,5,13,20,21,23), CXC (8,9,10,11,16), CX3CL1 (fractalkine), and GDF15. Adiponectin (an indicator of PPAR activation) and maresin 1 are reduced in SSc patients. A new trend has been the use of biomarker panels with combined complex multifactor analysis, machine learning, and artificial intelligence to determine disease activity and response to therapy. The present review is an update of the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

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Increased malignancies in systemic sclerosis

Cited by 4 publications

References 8 publications

Biomarkers in Systemic Sclerosis: An Overview

Biomarkers in Systemic Sclerosis: An Overview

Tree shrews as a new animal model for systemic sclerosis research

Biomarkers in the Pathogenesis, Diagnosis, and Treatment of Systemic Sclerosis

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