Background/Purpose: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is difficult to manage due to the heterogeneous disease course. There is a high need for biomarkers to identify patients at high risk for ILD progression. Fibroblast activation protein (FAP) has gained interest as a biomarker to reflect fibrotic activity. As circulating FAP (cFAP) can be measured in blood, we aimed to investigate the value of cFAP in SSc-ILD.

Methods: cFAP concentrations were determined in plasma samples of 210 SSc patients and 13 controls using an enzyme-linked immunosorbent assay. We compared cFAP levels in (repeated longitudinal) samples between SSc patients, with and without ILD (n=63 and n=147, respectively) and controls. Furthermore, we investigated the correlation between cFAP and ILD progression at follow-up (defined as forced vital capacity (FVC) decline ≥5%). In an exploratory analysis, we also investigated if cFAP was associated with other disease-related clinical features and all-cause mortality.

Results: cFAP levels were not different between SSc patients, with and without ILD, both at baseline (median 91.5 and 97.7 ng/mL; p >0.99) or during follow-up (Figure 1). Additionally, no differences were found between the cFAP levels of SSc patients, with or without ILD, and controls (median 76.9 ng/mL; p=0.08 and p=0.14). Furthermore, we found no correlations between cFAP at baseline and ILD progression at 1, 2 and 5 years of follow-up (Table 1 and Figure 2). In the entire SSc cohort, cFAP levels were elevated at baseline in patients with higher skin scores (mRSS ≥10 compared to mRSS < 10; p=0.01). Lastly, there was no association between cFAP and all-cause mortality at 5 and 10 years of follow-up.

Conclusion: In conclusion, cFAP does not seem useful as a biomarker in SSc-ILD. The relationship between cFAP and skin deserves additional investigation.

Figure 1. cFAP levels in patients with SSc – with and without ILD – and controls

Figure 2. cFAP concentrations plotted over time in SSc patients that did or did not develop ILD progression at 1, 2 and 5 years of follow-up

Table 1. Baseline cFAP is not associated with ILD progression during follow-up

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/longitudinal-assessment-of-circulating-fibroblast-activation-protein-in-systemic-sclerosis-associated-interstitial-lung-disease/