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Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging

Objectives To date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease. - Methods In this cross-sectional clinical st...

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Hauptverfasser: Schmidkonz, Christian (VerfasserIn) , Rauber, Simon (VerfasserIn) , Atzinger, Armin (VerfasserIn) , Agarwal, Rahul (VerfasserIn) , Götz, Theresa (VerfasserIn) , Soare, Alina (VerfasserIn) , Cordes, Michael (VerfasserIn) , Prante, Olaf (VerfasserIn) , Bergmann, Christina (VerfasserIn) , Kleyer, Arnd (VerfasserIn) , Ritt, Philipp (VerfasserIn) , Maschauer, Simone (VerfasserIn) , Hennig, Peter (VerfasserIn) , Toms, Johannes (VerfasserIn) , Köhner, Markus (VerfasserIn) , Manger, Bernhard (VerfasserIn) , Stone, John H. (VerfasserIn) , Haberkorn, Uwe (VerfasserIn) , Bäuerle, Tobias (VerfasserIn) , Distler, Jörg Hans Wilhelm (VerfasserIn) , Agaimy, Abbas (VerfasserIn) , Kuwert, Torsten (VerfasserIn) , Schett, Georg (VerfasserIn) , Ramming, Andreas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 July 2020
In: Annals of the rheumatic diseases
Year: 2020, Jahrgang: 79, Heft: 11, Pages: 1485-1491
ISSN:1468-2060
DOI:10.1136/annrheumdis-2020-217408
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/annrheumdis-2020-217408
Verlag, lizenzpflichtig, Volltext: https://ard.bmj.com/content/79/11/1485
Volltext
Verfasserangaben:Christian Schmidkonz, Simon Rauber, Armin Atzinger, Rahul Agarwal, Theresa Ida Götz, Alina Soare, Michael Cordes, Olaf Prante, Christina Bergmann, Arnd Kleyer, Philipp Ritt, Simone Maschauer, Peter Hennig, Johannes Toms, Markus Köhner, Bernhard Manger, John H.Stone, Uwe Haberkorn, Tobias Baeuerle, Jörg HW Distler, Abbas Agaimy, Torsten Kuwert, Georg Schett, Andreas Ramming
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Zusammenfassung:Objectives To date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease. - Methods In this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG4-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68Ga-FAP inhibitor (FAPI)-04), 18F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, 18F-FDG and 68Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data. - Results Using combination of 68Ga-FAPI-04 and 18F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG4 + cells in histology, while 68Ga-FAPI-04 PET positive lesions showed abundant activated fibroblasts expressing FAP according to results from RNA-sequencing of activated fibroblasts. The responsiveness of fibrotic lesions to anti-inflammatory treatment was far less pronounced than that of inflammatory lesions. - Conclusion FAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG4-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG4-related disease, as subtypes dominated by fibrosis may require different approaches to control disease progression, for example, specific antifibrotic agents rather than broad spectrum anti-inflammatory treatments such as glucocorticoids.
Beschreibung:Gesehen am 12.01.2021
Beschreibung:Online Resource
ISSN:1468-2060
DOI:10.1136/annrheumdis-2020-217408

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