NKG2D ligands in inflammatory joint diseases: analysis in human samples and mouse models.

OBJECTIVE

Ankylosing spondylitis (AS) is a progressive spinal disease presented as rheumatoid factor negative. As an autoimmune disorder, AS is featured with an inflammatory change of tendon and ligament, accompanied by elevates serum levels of inflammatory factors. MicroRNA (miR) participates in the regulation of various diseases including tumor, inflammation, cardiovascular disease and immune response. MiR16a exerts critical roles in inflammatory disease. Its function in AS, however, has not been fully illustrated.

PATIENTS AND

METHODS

AS patients (at stable and active phase) and healthy controlled individuals were recruited to test peripheral expression of miR16a by Real-time PCR (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test serum helper T cell 1 (Th1) cytokine levels including interferon (IFN)-γ, tumor necrosis factor-α (TNF-α) and Th2 cytokines including interleukin-4 (IL-4) and IL-10. The correlations between miR16a and cytokine levels, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and AS activity, were analyzed.

RESULTS

MiR16a expression in peripheral blood of AS patients was significantly higher compared to control people (p<0.05 compared to control group). AS patients at active phase had significantly higher miR16a levels, compared to stable phase (p<0.05). Serum IL-4 and IL-10 levels in AS patients were significantly increased, while IFN-γ and TNF-α expressions were depressed (p<0.05 compared to healthy controls). MiR16a expression was positively correlated with IL-4/IL-10 or disease active index, and was negatively correlated with IFN-γ and TNF-α levels (p<0.05), but not with CRP or ESR.

CONCLUSIONS

Peripheral miR16a was up-regulated in AS patients, and reflected disease activity, probably via regulating Th1/Th2 balance.