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

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

Book Volume: 79

Pages Range: 1485-1491

Journal Issue: 11

DOI: 10.1136/annrheumdis-2020-217408

Abstract

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.

Authors with CRIS profile

Christian Schmidkonz Medizinische Fakultät Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Armin Atzinger Department of Nuclear Medicine Rahul Agarwal Department of Medicine 3 – Rheumatology and Immunology Michael Cordes Medizinische Fakultät Olaf Prante Professur für Molekulare Bildgebung und Radiochemie Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Philipp Ritt Department of Nuclear Medicine Simone Maschauer Department of Nuclear Medicine Johannes Toms Department of Nuclear Medicine Bernhard Manger Professur für Rheumatologie und Klinische Immunologie Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Torsten Kuwert Lehrstuhl für Klinische Nuklearmedizin Georg Schett Lehrstuhl für Innere Medizin III Andreas Ramming Medizinische Fakultät

Involved external institutions

Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

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

MLA:

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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