Analysis of rheumatoid- vs psoriatic arthritis synovial fluid reveals differential macrophage (CCR2) and T helper subsets (STAT3/4 and FOXP3) activation.

Objective: In psoriatic arthritis (PsA) and rheumatoid arthritis (RA), inflammatory responses are characterized by increased production of pro-inflammatory molecules secreted by various immune cells. The main objectives of our study were: i) to measure levels of pro- and anti-inflammatory cyto-chemokines and soluble factors expressed in both PsA and RA SF; ii) to characterize the phenotype of infiltrated leuko-lymphocytes and; iii) to identify specific synovial biomarkers for both diseases. Notably, Synovial Fluid (SF) samples obtained from PsA and RA populations were compared with SF samples collected from clinically active osteoarthritis (OA) joints. Methods: SF samples were collected from clinically active knee arthritis of PsA, RA and OA patients and assayed for cyto-chemokines profile and macrophage and T helper subsets markers and transcriptional factors by Elisa Spot and western blot. Results: our study revealed that modulation of CCL-2, G-CSF, IL-1 beta and TNF-alpha is peculiar and specific to RA synovial fluid, whereas we detected more significant levels of ICAM-1, IL-2, IL-6, IL-17A, C5a and CXCL-9/12 in PsA compared to RA patients. We also found that CCR2 expression appeared to be significantly upmodulated in PsA and, even more, in RA group, as well as the expression of specific Th and Treg transcriptional factors as STAT3/4 and FOXP3. Conclusion: Even though this study has several limitations, we identified a heterogenous scenario of peculiar molecular pathway and soluble mediators' production that characterize PsA and RA SF that may be useful in understanding the complex pattern of macrophages and lymphocytes infiltration in both pathologies and, potentially, pave the way for personalized precision therapies.

Automated summary

This study compared the expression levels of cyto-chemokines in PsA and RA synovial fluid, finding unique and specific modulation of CCL-2, G-CSF, IL-1 beta, and TNF-alpha in RA synovial fluid, and significantly higher levels of ICAM-1, IL-2, IL-6, IL-17A, C5a, and CXCL-9/12 in PsA patients. The expression of CCR2 was significantly upregulated in both PsA and RA groups, along with specific Th and Treg transcription factors such as STAT3/4 and FOXP3.