Background: SAPHO syndrome, characterised by a variable combination of Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis, is a rare, often unrecognised disease with prominent inflammatory cutaneous and articular features. Recent evidences lead to consider SAPHO in the spectrum of Auto-Inflammatory Diseases(AID). Treatments with steroids, NSAIDS or TNF-a antagonists have been effectively employed. In humans, a key role of IL-1b as a pro-inflammatory regulator in the priming and differentiation of TH17 lineage and the central role of IL-1b hypersecretion in AID is well established. In some AID IL-1b has been implicated to lead towards a severe systemic inflammatory syndrome, possibly mediated by a TH17 skewed phenotype. The inflammatory P2X7-IL1b axis has been previously shown to be dysregulated in SAPHO syndrome. Method: We checked if the IL-1b derangement observed in SAPHO syndrome could affect the peripheral TH1, TH2 or TH17 frequency, in comparison with groups of healthy individuals and rheumatic disease controls, which were matched for sex, age, disease duration and treatment status. Results: TH17 levels for the two groups of SAPHO and not-SAPHO patients are significantly different (P = 0.009). We also studied the interaction between the variables SAPHO and treatment by means of a Fisher′s exact test which showed no significative dependence. TH1 and TH2 levels for the two groups of SAPHO and not-SAPHO patients are not significantly different. SAPHO patients showed significantly increased numbers of IL-17 producing T cells by flow-cytometry after PMA/ionomycin stimulation as compared to healthy controls. The frequency of TH17 cells between SAPHO patients and rheumatic controls, matched for sex, age, disease status and treated with the same drug (Methotrexate plus Adalimumab) was significantly increased, irrespectively of disease status or treatment. We observed no correlation between TH1 or TH2 and TH17. Conclusion: Our results suggest that activation of TH17 axis, but not of TH1 and TH2, is characteristic of SAPHO syndrome with protracted course, and that this finding is independent from remission status and/or from concurrent treatment with DMARDs or anti-TNF-a. Our preliminary data shed light on the possible involvement of TH17 cells in the immunopathogenesis of SAPHO, irrespectively from the patient′s disease status. Targeting IL-1b or IL-17 blockade may be considered in SAPHO patients on the basis of these results.

Increased peripheral T(H)17 Cells in SAPHO syndrome: a novel target for treatment?

FIRINU, DAVIDE;CABRAS, STEFANO;MANCONI, PAOLO EMILIO;DEL GIACCO, STEFANO
2013-01-01

Abstract

Background: SAPHO syndrome, characterised by a variable combination of Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis, is a rare, often unrecognised disease with prominent inflammatory cutaneous and articular features. Recent evidences lead to consider SAPHO in the spectrum of Auto-Inflammatory Diseases(AID). Treatments with steroids, NSAIDS or TNF-a antagonists have been effectively employed. In humans, a key role of IL-1b as a pro-inflammatory regulator in the priming and differentiation of TH17 lineage and the central role of IL-1b hypersecretion in AID is well established. In some AID IL-1b has been implicated to lead towards a severe systemic inflammatory syndrome, possibly mediated by a TH17 skewed phenotype. The inflammatory P2X7-IL1b axis has been previously shown to be dysregulated in SAPHO syndrome. Method: We checked if the IL-1b derangement observed in SAPHO syndrome could affect the peripheral TH1, TH2 or TH17 frequency, in comparison with groups of healthy individuals and rheumatic disease controls, which were matched for sex, age, disease duration and treatment status. Results: TH17 levels for the two groups of SAPHO and not-SAPHO patients are significantly different (P = 0.009). We also studied the interaction between the variables SAPHO and treatment by means of a Fisher′s exact test which showed no significative dependence. TH1 and TH2 levels for the two groups of SAPHO and not-SAPHO patients are not significantly different. SAPHO patients showed significantly increased numbers of IL-17 producing T cells by flow-cytometry after PMA/ionomycin stimulation as compared to healthy controls. The frequency of TH17 cells between SAPHO patients and rheumatic controls, matched for sex, age, disease status and treated with the same drug (Methotrexate plus Adalimumab) was significantly increased, irrespectively of disease status or treatment. We observed no correlation between TH1 or TH2 and TH17. Conclusion: Our results suggest that activation of TH17 axis, but not of TH1 and TH2, is characteristic of SAPHO syndrome with protracted course, and that this finding is independent from remission status and/or from concurrent treatment with DMARDs or anti-TNF-a. Our preliminary data shed light on the possible involvement of TH17 cells in the immunopathogenesis of SAPHO, irrespectively from the patient′s disease status. Targeting IL-1b or IL-17 blockade may be considered in SAPHO patients on the basis of these results.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/59858
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