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Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.
Methods: We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n=102), among which SSc-no ILD (n=63) and SSc-ILD (n=39), compared to healthy subjects (HS) (n=39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts.
Results: Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r=0.6, p<0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2<105 ng/ml was associated with a better outcome (low risk to display KCO<70% predicted) at 2-year follow-up (area under the curve=0.75 at 75% sensibility and 68% specificity, p<0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.
Conclusions: We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.
Keywords
IGF pathway, systemic sclerosis, interstitial lung disease, lung fibrosis, biomarkers.
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1Guiotetal.pdf
Table S1. Serum variation of biomarkers between baseline and 2-year follow-up.
- Additionalfile1Guiotetal.pdf
Table S1. Serum variation of biomarkers between baseline and 2-year follow-up.
- Additionalfile2Guiotetal.pdf
Table S2. Correlation between biomarkers and pulmonary function tests at 2-year follow-up.
- Additionalfile2Guiotetal.pdf
Table S2. Correlation between biomarkers and pulmonary function tests at 2-year follow-up.
- Additionalfile3Guiotetal.pdf
Additional file 3: Supplementary Figure S1. Method used to assess the better cut-off point.
- Additionalfile3Guiotetal.pdf
Additional file 3: Supplementary Figure S1. Method used to assess the better cut-off point.
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 15 Dec, 2020
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.
Methods: We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n=102), among which SSc-no ILD (n=63) and SSc-ILD (n=39), compared to healthy subjects (HS) (n=39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts.
Results: Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r=0.6, p<0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2<105 ng/ml was associated with a better outcome (low risk to display KCO<70% predicted) at 2-year follow-up (area under the curve=0.75 at 75% sensibility and 68% specificity, p<0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.
Conclusions: We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1Guiotetal.pdf
Table S1. Serum variation of biomarkers between baseline and 2-year follow-up.
- Additionalfile1Guiotetal.pdf
Table S1. Serum variation of biomarkers between baseline and 2-year follow-up.
- Additionalfile2Guiotetal.pdf
Table S2. Correlation between biomarkers and pulmonary function tests at 2-year follow-up.
- Additionalfile2Guiotetal.pdf
Table S2. Correlation between biomarkers and pulmonary function tests at 2-year follow-up.
- Additionalfile3Guiotetal.pdf
Additional file 3: Supplementary Figure S1. Method used to assess the better cut-off point.
- Additionalfile3Guiotetal.pdf
Additional file 3: Supplementary Figure S1. Method used to assess the better cut-off point.
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