Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis

Oller-Rodríguez, José Eloy; Bernabéu, E. Vicens; González-Mazarío, Roxana; García, Elena Grau; Sanjuán, Francisco Miguel Ortíz; Ivorra, José Andrés Román

doi:10.1016/j.medcli.2021.12.006

Cited by 8 publications

(11 citation statements)

References 28 publications

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“…In addition, patients with GDF-15 levels below this threshold had significantly better survival rates. This finding was corroborated in a recent study, which found higher GDF-15 levels in SSc patients vs. those in healthy controls and a significant association between elevated GDF-15 and PH in SSc patients [ 54 ].…”

Section: Endothelial Dysfunctionsupporting

confidence: 82%

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Moccaldi

Michieli

Binda

et al. 2023

IJMS

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Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies—except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended—CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease.

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Section: Endothelial Dysfunctionsupporting

confidence: 82%

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Moccaldi

Michieli

Binda

et al. 2023

IJMS

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“…Serum concentrations of CXCL11, reported to be raised in early SSc patients when compared with healthy individuals, strongly associated with disease activity [ 190 ], while pro-angiogenic CXCL16 was elevated in SSc, particularly in patients with PAH [ 189 , 190 ]. Recently, when measuring circulating levels of CXCL4, CXCL8, and GDF15, a small chemokine belonging to the TGF-β superfamily, in another cohort of SSc patients, only GDF15 was found to be higher in SSc and to associate with PAH and dilated capillary loops at capillaroscopy [ 191 ].…”

Section: Cytokinesmentioning

confidence: 99%

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Fioretto

Rosa

Matucci‐Cerinic

et al. 2023

IJMS

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Systemic sclerosis (SSc, scleroderma) is a multifaceted rare connective tissue disease whose pathogenesis is dominated by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and both cutaneous and visceral fibrosis. Microvascular impairment represents the initial event of the disease, preceding fibrosis by months or years and accounting for the main disabling and/or life-threatening clinical manifestations, including telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy, ischemic digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. Despite a variety of available treatment options, treatment of SSc-related vascular disease remains problematic, even considering SSc etherogenity and the quite narrow therapeutic window. In this context, plenty of studies have highlighted the great usefulness in clinical practice of vascular biomarkers allowing clinicians to assess the evolution of the pathological process affecting the vessels, as well as to predict the prognosis and the response to therapy. The current narrative review provides an up-to-date overview of the main candidate vascular biomarkers that have been proposed for SSc, focusing on their main reported associations with characteristic clinical vascular features of the disease.

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Section: Biomarkers In Systemic Sclerosis Vascular Injury Focus On Pu...mentioning

confidence: 99%

“…Local secretion of the von Willebrand factor causes platelet aggregation, hypercoagulability, and fibrin deposition leading to terminal vascular injury [126][127][128][129][130][131][132][133]151]. The endothelialmesenchymal transition also favors the formation of myofibroblasts [128][129][130][131][132][133]152,153]. The activated endothelium also expresses an increase in adhesion molecules and specific chemokines, recruiting immune cells and perivascular infiltrates leading to further inflammation and fibrosis [128][129][130][131][132][133]152,153].…”

Section: Biomarkers In Systemic Sclerosis Vascular Injury Focus On Pu...mentioning

confidence: 99%

“…The endothelialmesenchymal transition also favors the formation of myofibroblasts [128][129][130][131][132][133]152,153]. The activated endothelium also expresses an increase in adhesion molecules and specific chemokines, recruiting immune cells and perivascular infiltrates leading to further inflammation and fibrosis [128][129][130][131][132][133]152,153]. Specifically, the imbalance of cytokines, including endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-9, endoglin, endothelin-1 (ET-1), and the angiostatic pentraxin 3 (PTX3), MMP-12, endostatin, angiostatin and semaphorin3E (Sema3E) cause dysfunction in angiogenesis and an alteration in endothelial progenitor cell (EPC) recruitment [116][117][118][119].…”

Section: Biomarkers In Systemic Sclerosis Vascular Injury Focus On Pu...mentioning

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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Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis

Cited by 8 publications

References 28 publications

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Biomarkers in Systemic Sclerosis: An Overview

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