Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging
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- 21 July 2020
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 79 (11), 1485-1491
- https://doi.org/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 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.Keywords
Funding Information
- H2020 European Research Council (BARRIER BREAK 853508)
- Wilhelm Sander-Stiftung (2017.129.1)
- Interdisciplinary Centre for Clinical Research, Erlangen (D34)
- Bundesministerium für Bildung und Forschung (13N 13341 to U.H., MASCARA to J.H.W.D., G.S., T.K., A.R.)
- ELAN Fonds of the Universitätsklinikum Erlangen (17-11-20-1 to A.S.)
- Deutsche Forschungsgemeinschaft (CRC1181 to G.S. (project A01), J.H.W.D. (project C, RA 2506/4-1, RA 2506/4-2, RA 2506/6-1, SCHE 1583/7-1, SO 1735/2-1)
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