Abstract The use of immunosuppressive therapies for rheumatoid arthritis (RA) is associated with substantial adverse effects. In addition, existing diagnostic reagents are limited in their ability to detect local joint damage. Here, we address both these needs using a collagen-hybridizing peptide (CHP) that selectively binds denatured collagen present in inflamed joints in RA models. Light-sheet scanning and immunohistology of the inflamed ankles in RA mice pre-injected with fluorescently-labeled-CHP revealed specific CHP accumulation within matrices of the synovial pannus and cartilage that express matrix metalloproteases and cathepsin K extensively. In vivo fluorescence probing with labeled CHP enabled dynamic monitoring of collagen breakdown throughout RA progression or regression with sensitivity beyond arthritis scoring. Moreover, bioconjugation of a therapeutic monoclonal antibody (mAb) against TNF with CHP enriched the mAb precisely within the pannus of inflamed joints in RA mice, resulting in improved efficacy relative to the native mAb and reduced systemic exposure. These findings highlight denatured collagen as a molecular matrix signature of RA lesions for diagnostic imaging and an effective target for RA drug delivery.
Mo et al. (Mon,) studied this question.