• Martin Kaae Kristiansen
Introduction: Arthritis is a broad clinical term that includes many different joint diseases of different etiology. The most common type is osteoarthritis, which is treated with NSAIDs and glucocorticoids to manage pain and dampen inflammation. However, most current treatment options are systemic with potential systemic adverse effects. A new possible treatment to overcome this is intra articular gold microparticle implants which is thought to inhibit articular inflammation in several ways, sch as inhibition of the NF-kB pathway. The most common autoimmune type of arthritis is rheumatoid arthritis, and despite a different pathogenesis than OA, inflammation also plays a major role in in RA, and the main goal of treatment is also here to decrease the inflammatory status and manage pain. Like in OA, NSAIDs and glucocorticoids are used in RA treatment along with DMARDs and bDMARDs which all have potential systemic adverse effects as well.
Aim: The aims of this study are to elucidate the supposed mode of action and anti-inflammatory potential of gold microparticles as a treatment of OA. Proteomic profiling of synovial fluid and serum samples before and after treatment were performed to investigate this novel treatment’s impact on inflammation. Another aim is to search for biomarkers in gold treated patients to monitor treatment effect, and to enable the possibility for a personalized treatment. Furthermore, serum samples before and after RA treatment with etanercept will also be analyzed to look for similarities in inflammatory status that could suggest a possible effect of gold particles in the treatment of RA.
Methods: Paired biological samples from 29 OA patients were collected pre- and 8 weeks post treatment with gold particles. These were analyzed using quantitative proteomics, innate immune regulatory cfDNA-measurement, and cytokine profiling to evaluate inflammatory status before and after treatment. Paired biological samples from 18 RA patients before and after treatment with etanercept were also analyzed with proteomics and cfDNA-measurement as well and correlated to the results of OA gold treatment.
Results: 24 immunologically associated molecules identified by PEA were significantly downregulated following gold treatment of OA. Several of these have direct correlations to both OA, RA, inflammation, and the NF-kB pathway. MS found 22 proteins to be significantly regulated in OA, several of which can be correlated with OA, RA, inflammation, and NF-kB as well. cfDNA did not show a significant drop following eight weeks of OA gold treatment, but other studies and observations indicate that 8 weeks might not be enough time to elicit the full effect of a gold treatment.
Conclusions: The clinically observed effects of an OA gold treatment found basis in the observed proteomic changes identified in this study, in respect to both decreased inflammatory markers, modulation of NF-kB and connection to OA pathology. These effects coupled with the proteomic data and knowledge of an RA pathogenesis, opens the possibility of positive effects by gold microparticle treatment of RA as well.
Publication date28 May 2020
Number of pages42
ID: 333156014