Circulating biomarkers of systemic sclerosis – interstitial lung disease

Abstract

Interstitial lung disease is a frequent organ manifestation in systemic sclerosis and is associated with high mortality. It is crucial to diagnose interstitial lung disease in systemic sclerosis and to assess severity and identify patients prone to progression at an early stage to ultimately decrease organ damage and improve outcome. Circulating anti-topoisomerase-I autoantibodies have long been associated with the presence and development of systemic sclerosis – interstitial lung disease, evidence on their potential to further predict the clinical course of systemic sclerosis is however conflicting. C-reactive protein is a marker of infection and systemic inflammation with widespread clinical application and is elevated in systemic sclerosis with a tendency towards higher abundancy in patients with early disease. The role of other circulating biomarkers is promising but hampered by the lack of standardized criteria and guidelines for sample/data collection, analyses, reporting and validation and has not reached prime time for clinical application. However, epithelial markers including Krebs von den Lungen-6 and surfactant protein D and several cytokines and chemokines including CCL2 and CCL18 for severity assessment of systemic sclerosis – interstitial lung disease patients at the time of interstitial lung disease diagnosis and to predict interstitial lung disease progression have been reported and seem to be promising candidate biomarkers in the future.

Serum metabolites as biomarkers in systemic sclerosis-associated interstitial lung disease

“…Currently available measures such as imaging, pulmonary function tests, or patient reported outcome scores have been shown to be of limited predictive value for the identification of SSc-ILD patients with poor prognosis 6 , 7 . Circulating biomarkers as readily available tools have been studied extensively with focus on serum proteins and auto-antibodies, but have not yet been established for daily use 8 .…”

The Treatment of Lung Involvement in Systemic Sclerosis

“…Although consensus and recommendations are nowadays available, these do not fully cover the different clinical scenarios, in particular regarding time to initiation and a possibly more effective treatment protocol. In this context, SSc experts still relay on their clinical experience and take into account the different abovementioned factors to guide their decision in a patient-tailored, customized treatment regimen [ 89 ], possibly informed also by molecular biomarkers [ 90 ].…”

Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics

“…Recent data challenge this convention demonstrating that even patients with mild SSc-ILD (lung fibrosis extent on HRCT <10%, FVC 80-100%) frequently developed progressive ILD with reduced survival 26 . The lack of prognostic and independently validated biomarkers 38,39 , which could be met by the recent advances in image acquisition, processing, and high-throughput image analysis, have prompted the herein presented study. Here, we report four key findings: 1) We confirm the reproducibility of radiomic features with respect to tissue segmentation and identify 1,355 stable radiomic features for SSc-ILD.…”

“…The lack of prognostic and independently validated biomarkers 38,39 , which could be met by the recent advances in image acquisition, processing, and high-throughput image analysis, have prompted the herein presented study.…”