Department of Nuclear Medicine, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany.
Department of Internal Medicine 3, Rheumatology & Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany.
Ann Rheum Dis. 2020 Nov;79(11):1485-1491. doi: 10.1136/annrheumdis-2020-217408. Epub 2020 Jul 21.
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-related disease.
In this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; Ga-FAP inhibitor (FAPI)-04), F-fluorodeoxyglucose (FDG), MRI and histopathological assessment. In a longitudinal approach, F-FDG and Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data.
Using combination of Ga-FAPI-04 and F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG cells in histology, while 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.
FAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG-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.
迄今为止，尚无有价值的工具能够在体内无创地评估纤维化疾病的活动。本研究旨在将纤维炎症性疾病（如 IgG 相关疾病）中的炎症与纤维化疾病活动区分开来。
在这项横断面临床研究中，27 例具有 IgG 相关疾病炎症、纤维化和重叠表现的患者接受了特定于成纤维细胞激活蛋白（FAP；Ga-FAP 抑制剂（FAPI）-04）、F-氟脱氧葡萄糖（FDG）、MRI 和组织病理学评估的正电子发射断层扫描（PET）。在纵向研究中，评估了免疫抑制治疗前后的 F-FDG 和 Ga-FAPI-04 PET/CT 数据，并将其与临床和 MRI 数据相关联。
使用 Ga-FAPI-04 和 F-FDG-PET 的组合，我们证明了从炎症向纤维化结果的 IgG 相关疾病演变的非侵入性功能追踪成为可能。F-FDG-PET 阳性病变在组织学上显示 IgG 细胞的密集淋巴浆细胞浸润，而 Ga-FAPI-04 PET 阳性病变根据激活成纤维细胞的 RNA 测序结果显示大量表达 FAP 的激活成纤维细胞。纤维化病变对抗炎治疗的反应远不如炎症病变明显。
FAP 特异性 PET/CT 可区分 IgG 相关疾病中的炎症和纤维化活动。这一发现可能会彻底改变某些形式的免疫介导性疾病的治疗方法，例如 IgG 相关疾病，因为纤维化为主的亚型可能需要不同的方法来控制疾病进展，例如，特异性抗纤维化药物而不是广泛的抗炎治疗，如糖皮质激素。
