MIF, TNF-α, and IL-6 concentrations in cell supernatants of AS PBMCs were significantly higher than those of pSpA and control PBMCs. miR-451 expression level did not show significant correlation with clinical parameters, but MIF expression level was elevated in PBMCs from AS patients with high mSASSS (12 or more).
Improved knowledge of the immune/inflammatory pathways, which characterise the pathophysiology of rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have provided the link between inflammation and bone loss, via a complex network of bone cells, T and B cells, pro-inflammatory cytokines such as TNF-α, IL1, IL6, IL17, IL23, costimulator molecules, signalling pathways including both RANKL/RANK/OPG and Wnt signallings.
Significantly higher baseline Th17 cells and serum IL-17, TNF-α and IL-6 were observed in AS patients than in normal controls, whereas baseline levels of Treg cells and serum IL-10 were not significantly different between AS patients and healthy controls.
We performed flow cytometry to assess the distribution of peripheral blood T cell subpopulations in the context of serum inflammatory markers (TNF-α, IL-6, sICAM-1) and asymmetric dimethylarginine (ADMA) in 38 patients with AS with active disease, and in 20 healthy controls.
Expression level of miR-146a in PBMC of AS patients was significantly higher than that of healthy control (P<0.01); levels of TNF-α, IL-1β and IL-6 in serum and the supernatant of culture medium of PBMC derived from AS patients were significant compared to those of control group (P<0.01); expression of miR-146a in PBMC of patients with AS was positively correlated with the levels of TNF-α, IL-1β and IL-6 in serum (r=0.632, P<0.01; r=0.574, P<0.01; r=0.483, P<0.01).
Stimulation of PBMCs by exogenous leptin significantly increased the production of IL-6 and TNF-alpha in PBMCs from patients with AS in a dose-dependent fashion and these increases were much exacerbated compared to controls.