Biomarkers of Scleroderma Lung Disease: Recent Progress

Hant, Faye N.; Silver, Richard M.

doi:10.1007/s11926-010-0143-9

Cited by 13 publications

(6 citation statements)

References 45 publications

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“…These efforts have led to a number of candidate molecules and scoring systems (reviewed in Refs. 25, 48). They also highlighted the importance of biomarker validity and reproducibility, the ability of the biomarker to discriminate between the situations of interest, and the feasibility of biomarker evaluation (25).…”

Section: Discussionmentioning

confidence: 99%

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

Lee

Herzog

Ahangari

et al. 2012

The Journal of Immunology

113

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Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling.

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Section: Discussionmentioning

confidence: 99%

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

Lee

Herzog

Ahangari

et al. 2012

The Journal of Immunology

113

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“…As elegantly reviewed by Hant and Silver, serum levels of PMN elastase have been reported as significantly increased in SSc-ILD and interestingly correlated well with SP-D and KL-6 [15, 86]. …”

Section: Neutrophil Elastasementioning

confidence: 99%

“…Biomarkers can fulfil a number of roles, including identification of pathways involved in disease pathogenesis, assessment of disease severity, prediction of future disease behaviour and use as surrogate outcome measures [15]. This paper focuses on peripheral blood biomarkers, as they offer a number of advantages—they are readily obtained, can be measured longitudinally, and thus have the potential to be integrated into clinical use.…”

Section: Introductionmentioning

confidence: 99%

Circulating Biomarkers of Interstitial Lung Disease in Systemic Sclerosis

Lota

Renzoni

2012

International Journal of Rheumatology

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Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.

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“…Some studies referred lung injury as the initial change. In response, bronchiolar epithelial and alveolar cells produce and secrete more SP-D, which is a member of collagenase subfamily of collectin, participating in a range of innate immune and inflammatory responses [43,44]. In the same way, the biomarker KL-6, a human MUC1 mucin secreted by type II pneumocytes, is over produced.…”

Section: Possible Biomarksmentioning

confidence: 99%

Interstitial Lung Disease in Scleroderma: Clinical Features and Pathogenesis

Luo¹,

Xiao²

2012

Rheumatology

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Interstitial lung disease is a prevalent but worrisome implication in scleroderma. It is now the leading cause of morbidity and mortality since the dramatic reduction in death caused by scleroderma renal crisis. However, the pathogenesis remains unknown. Most observers suggest that lung injury induces microvascular damage and immunologically-mediated inflammation. As oxidative stress and leukotrienes-lipoxins imbalance is observed in-ILD patients, a series of proinflammatory and profibrotic cytokines are also found. Possible biomarkers including SP-D, KL-6, Caveolin-1, IL-6, IL-1 may be useful index for diagnosis and progression, which also suggest the potential mechanism. There are also some studies focusing the relationship between gastroesophageal reflux (GER) and SSc-ILD, which partly explain the mechanism from a new perspective.

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Biomarkers of Scleroderma Lung Disease: Recent Progress

Cited by 13 publications

References 45 publications

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

Circulating Biomarkers of Interstitial Lung Disease in Systemic Sclerosis

Interstitial Lung Disease in Scleroderma: Clinical Features and Pathogenesis

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