Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging

Schmidkonz C, Rauber S, Atzinger A, Agarwal R, Götz TI, Soare A, Cordes M, Prante O, Bergmann C, Kleyer A, Ritt P, Maschauer S, Hennig P, Toms J, Köhner M, Manger B, Stone JH, Haberkorn U, Bäuerle T, Distler J, Agaimy A, Kuwert T, Schett G, Ramming A (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 79

Pages Range: 1485-1491

Journal Issue: 11

DOI: 10.1136/annrheumdis-2020-217408


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 IgG 4 -related disease. Methods In this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG 4 -related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68 Ga-FAP inhibitor (FAPI)-04), 18 F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, 18 F-FDG and 68 Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data. Results Using combination of 68 Ga-FAPI-04 and 18 F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG 4 -related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18 F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG 4 + cells in histology, while 68 Ga-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 IgG 4 -related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG 4 -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.

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Schmidkonz, C., Rauber, S., Atzinger, A., Agarwal, R., Götz, T.I., Soare, A.,... Ramming, A. (2020). Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging. Annals of the Rheumatic Diseases, 79(11), 1485-1491. https://doi.org/10.1136/annrheumdis-2020-217408


Schmidkonz, Christian, et al. "Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging." Annals of the Rheumatic Diseases 79.11 (2020): 1485-1491.

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