期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 79, 期 11, 页码 1485-1491出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2020-217408
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资金
- Deutsche Forschungsgemeinschaft [RA 2506/4-1, RA 2506/4-2, RA 2506/6-1, SO 1735/2-1, DI 1537/14-1, SCHE 1583/7-1, CRC1181, (C06)]
- European Research Council [853 508]
- ERC Synergy grant 4D Nanoscope
- Bundesministerium fur Bildung und Forschung (MASCARA)
- Interdisciplinary Centre for Clinical Research, Erlangen [D34]
- IZKF Fonds of the Universitatsklinikum Erlangen [17-11-20-1]
- Federal Ministry of Education and Research [13N 13341]
- ELAN [17-11-20-1]
- Wilhelm Sander--Stiftung [2017.129.1]
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; Ga-68-FAP inhibitor (FAPI)-04), F-18-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, F-18-FDG and Ga-68-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data. Results Using combination of Ga-68-FAPI-04 and F-18-FDG-PET, we demonstrate that non-invasive functional tracking of IgG 4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. F-18-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG(4)(+) cells in histology, while Ga-68-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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