Background/Purpose:

Ankylosing spondylitis (AS) is chronic inflammatory disease of unknown origin.  Studies into the molecular basis of AS  have demonstrated  exaggerated innate and adaptive immune responses mediated though various cytokines. Over-expression of  cytokines such as TNF–α and IL-17 – has provided  a rationale for targeted biologic agents for  suppressing the disease activity. Identifying the cellular sources of these cytokines is crucial to understand the pillars of inflammation in AS. Recently;, mucosal associated invariant T (MAIT)-cells have been implicated in various autoimmune diseases. Their effectors phenotype and preferential localization to peripheral tissue makes them possible contributor in the pathogenesis of AS . Thus we hypothesized that MAIT cells may be increased  in AS patients compared to normal controls.

Methods:

Peripheral blood mononuclear cells (PBMC) and synovial fluid (SF) mononuclear cells (SFMC) from the AS patients (N=17) and controls (n=11) were isolated, . Healthy controls were used for the MAIT cells in the in PBMC while RA and OA were used as controls for the SF  MAIT cells. Flow cytometry was used to identify MAIT cells, which were defined as CD3+CD161^hiV.α 7.2+CCR6+, with the majority being CD8+.  Cytokine production by respective cell populations  was assessed indirectly  by intracellular straining  for IL-4, IL-17, TNFa , IFNg  and granzyme B.

Results:

The percentage of MAIT cells in PBMC of AS patients and control groups were similar.   Whereas CD69+ (activation marker) and CCR6+(homing marker) MAIT cells were comparable in AS and HC,  CCR6+ MAIT showed a tendency to be higher  in AS PBMC. It  was noted that in PBMC, activated MAIT cells (CD69+) represented  a small proportion of the total MAIT cells in. In contrast,  almost all SF MAIT cells from AS patients were activated (CD69+). We also noticed that the percentage of CD4+ MAIT to total MAIT cells in AS SF  is higher than peripheral blood. Similar results were seen in paired patient blood-synovial fluid analysis. In this analysis,; IL17 production was similar while an increased granzyme B production and reduction of IL4, IFNγ and TNFα were detected in SF MAIT cells compared to MAIT cells in PBMC.

Conclusion:

To our knowledge, this study is the first to look at MAIT cells in both blood and SF of AS patients.ij. Interestingly MAIT cells  in the inflamed joints in AS are predominantly  activated.  This suggests that examining the microenvironment of the joint to define the activating signals for local MAIT cells would be productive.