CD64 as novel molecular imaging marker for the characterization of synovitis in rheumatoid arthritis.

Autor: Theeuwes WF; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Di Ceglie I; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Dorst DN; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands., Blom AB; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Bos DL; Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands., Vogl T; Institute of Immunology, University of Münster, Münster, Germany., Tas SW; Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and Immunology Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Jimenez-Royo P; Research and Development, GlaxoSmithKline, Stevenage, UK., Bergstrom M; Research and Development, GlaxoSmithKline, Stevenage, UK., Cleveland M; Bioimaging, In Vitro/In Vivo Translation (IVIVT), GlaxoSmithKline, Stevenage, UK., van der Kraan PM; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Laverman P; Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands., Koenders MI; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., van Lent PL; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., van den Bosch MHJ; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. Martijn.vandenbosch@radboudumc.nl.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2023 Aug 31; Vol. 25 (1), pp. 158. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1186/s13075-023-03147-y
Abstrakt: Background: Rheumatoid arthritis (RA) is one of the most prevalent and debilitating joint diseases worldwide. RA is characterized by synovial inflammation (synovitis), which is linked to the development of joint destruction. Magnetic resonance imaging and ultrasonography are widely being used to detect the presence and extent of synovitis. However, these techniques do not reveal the activation status of inflammatory cells such as macrophages that play a crucial role in synovitis and express CD64 (Fc gamma receptor (FcγR)I) which is considered as macrophage activation marker.
Objectives: We aimed to investigate CD64 expression and its correlation with pro-inflammatory cytokines and pro-damaging factors in human-derived RA synovium. Furthermore, we aimed to set up a molecular imaging modality using a radiolabeled CD64-specific antibody as a novel imaging tracer that could be used to determine the extent and phenotype of synovitis using optical and nuclear imaging.
Methods: First, we investigated CD64 expression in synovium of early- and late-stage RA patients and studied its correlation with the expression of pro-inflammatory and tissue-damaging factors. Next, we conjugated an anti-CD64 antibody with IRDye 800CW and diethylenetriamine penta-acetic acid (DTPA; used for 111 In labeling) and tested its binding on cultured THP1 cells, ex vivo RA synovium explants and its imaging potential in SCID mice implanted with human RA synovium explants obtained from RA patients who underwent total joint replacement.
Results: We showed that CD64 is expressed in synovium of early and late-stage RA patients and that FCGR1A/CD64 expression is strongly correlated with factors known to be involved in RA progression. Combined, this makes CD64 a useful marker for imaging the extent and phenotype of synovitis. We reported higher binding of the [ 111 In]In-DTPA-IRDye 800CW anti-CD64 antibody to in vitro cultured THP1 monocytes and ex vivo RA synovium compared to isotype control. In human RA synovial explants implanted in SCID mice, the ratio of uptake of the antibody in synovium over blood was significantly higher when injected with anti-CD64 compared to isotype and injecting an excess of unlabeled antibody significantly reduced the antibody-binding associated signal, both indicating specific receptor binding.
Conclusion: Taken together, we successfully developed an optical and nuclear imaging modality to detect CD64 in human RA synovium in vivo.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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