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Etarfolatide imaging may help identify FR-positive OA phenotype
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LIVERPOOL, England — Researchers identified six biomarkers in the synovial fluid of patients with OA that may be useful in stratification by risk or phenotype, according to findings presented here.
Janet L. Huebner, MS, Senior Laboratory Analyst and Manager of Biomarkers Shared Resource at the Duke Molecular Physiology Institute, and colleagues aimed to investigate the role of activated synovial macrophages in the inflammatory phenotype of OA. “Activated synovial macrophages have been shown to drive inflammatory responses in OA,” she said. In addition, recent findings have shown that folate receptor (FR)-positive macrophages and neutrophils have been associated with synovial fluid biomarkers predictive of knee OA progression, according to Huebner.
The purpose of the current study was to investigate the association of synovial fluid proinflammatory biomarkers with FR-positive etarfolatide uptake and OA severity. “We hypothesized that the identification of these biomarkers would provide a biological profile for identifying subjects with an inflammatory OA phenotype,” Huebner said.
The Folate study cohort included 25 participants, 72% of whom were female, with 76% having moderate to severe radiographic OA. The researchers obtained synovial fluid from 48 knees for the quantification of inflammatory biomarkers. Results of the etarfolatide imaging showed that 76% of knees were positive for FR-positive cells in the synovium of the joint.
Of 46 inflammatory biomarkers assessed, six synovial fluid biomarkers demonstrated significant associations with features associated with OA. These included MMP-3, sVCAM1, sICAM1, VEGF, TIMP-1 and MCP1 (CCL2)
Huebner presented a string diagram to describe how the synovial fluid biomarkers interact in the context of disease. She explained that MCP-1 (CCL2) is associated with macrophage recruitment, while VEGF is a mediator of new vessel formation (angiogenesis) that occurs during inflammation and the expansion of the synovial lining of the joint. Soluble VCAM1 and sICAM1 are increased in inflammatory diseases and are associated with synovitis. MMP-3 and TIMP-1 are important in the regulation of ECM turnover, Huebner added. “We can build a model that demonstrates how activated macrophages and neutrophils contribute to an inflammatory phenotype,” she said.
Huebner concluded that an FR-positive phenotype can be identified by etarfolatide imaging and/or synovial fluid cell characterization. “Both the activated macrophages and neutrophils in OA have been identified as being FR-positive cells,” she said. “These cells have been shown to play an important role in OA pain and radiographic severity. The identification of FR-positive phenotype of OA might be a way of selecting and monitoring patients who are either at high risk for progression, or for whom anti-inflammatory therapies may be appropriate.” – by Rob Volansky
Reference:
Huebner JL, et al. Abstract #62. Presented at: OARSI 2018 World Congress on Osteoarthritis; April 26-29, 2018; Liverpool, England.
Disclosure: Huebner reports no relevant financial disclosures.