Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome

Abstract

The aetiology of SAPHO (synovitis, acne, palmoplantar pustulosis, hyperostosis, osteitis) syndrome seems to involve genetic, infectious and immunological components. We examined innate and adaptive immune responses in SAPHO syndrome, as compared with PsA and RA. We also studied the effect of etanercept on immunological parameters. We studied 29 patients with SAPHO syndrome, as well as 22 patients with RA, 21 patients with PsA and 15 healthy controls. Adaptive immune responses were investigated by assaying total serum immunoglobulins and several autoantibodies. Innate immunity was studied by quantifying blood PMN functions and plasma cytokine levels. PMN responses to Propionibacterium acnes were tested ex vivo. Eight patients who received etanercept for refractory rheumatic disorders were tested before and after 28 days of treatment. SAPHO syndrome was associated with elevated IL-8 and IL-18 plasma levels. IL-8 and TNF-alpha production by purified PMN was higher in the three patient groups than in the healthy controls, but the oxidative burst and IL-18 production were normal. No autoantibodies were detected in SAPHO patients. Induction of PMN IL-8 and TNF-alpha production by P. acnes was impaired in the SAPHO group as compared with the RA and PsA groups. After 28 days of etanercept therapy, PMN IL-8 and TNF-alpha production was down-regulated and TNF-alpha plasma levels were increased. These results support the view that the SAPHO syndrome may be triggered by an infectious state involving P. acnes, contributing to the strong humoral and cellular pro-inflammatory responses. Etanercept modulation of PMN activation status emphasizes these new immunological findings.