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46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

19.09. - 22.09.2018, Mannheim

Different expression of TNF and interleukin 8 in polymorphic neutrophils (PMN) of SAPHO patients due to interleukin 17 blocking agent

Meeting Abstract

  • Gunter Assmann - José Carreras Center for Immuno- and Gene Therapy, University Medical School of Saarland, Department of Internal Medicine I, Homburg/Saar
  • Konstantinos Chrystophyllakis - University Saarland Medical School, Rheumatology, Hematology, Oncologie, Homburg
  • Claudia Schormann - University Saarland Medical School, Rheumatology, Hematology, Oncology, Homburg
  • Awal Tajali - Klinikum Püttlingen, Rheumatology and Immunology, Püttlingen
  • Michael Pfreundschuh - José Carreras Center for Immuno- and Gene Therapy, University Medical School of Saarland, Department of Internal Medicine I, Homburg/Saar
  • Frank Neumann - University Saarland Medical School, Jose Carreras Center of Immunogenetics and Gene-Therapy, Homburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Mannheim, 19.-22.09.2018. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocER.29

doi: 10.3205/18dgrh108, urn:nbn:de:0183-18dgrh1089

Veröffentlicht: 5. Februar 2019

© 2019 Assmann et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Background: The characteristic defining symptoms of SAPHO syndrome are synovitis, acne, palmoplantar pustolosis, and hyperostosis with osteitis. The SAPHO syndrome has to be considered as a rare subtype of the disease entity of seronegative spondyloarthritis (SpA). The etiology of SAPHO remains unclear so far; investigations of polymorphic neutrophils (PMN) derived from SAPHO patients resulted in in-vitro tests differences of immune response on antigen stimulation as well as zytokine proliferation compared to healthy controls, psoriatic arthritis or rheumatoid arthritis [1]. Furthermore, with the regard to T-cell immunology and SAPHO syndrome Firinu D et al. [2] has previously demonstrated higher count of TH-17 cells in the peripheral blood in patients with SAPHO syndrome compared to psoriatic arthritis and healthy controls.

Methods: Peripheral blood was derived from 4 patients with SAPHO syndrome of our outpatient rheumatology department. As controls served patients with psoriatic arthritis (PsA, n=4) and healthy controls (HC, n=4). The SAPHO patients fullfilled also the diagnostic criteria of seronegative SpA. SAPHO patients as well as psoriasis arthritis patients received treatment with IL17 blocking agent secukinumab 150 mg according to standard protocol for four months. Prior to treatment and after four months treatment with secukinumab the disease activity of patients was evaluated using HAQ score (SAPHO and PsA), DAS28 (for PsA), osteitis activity and skin activity (respectively, SAPHO, patients score 0-6). Moreover, the blood specimen prior as well as after treatment with secukinumab were separated in EDTA containing tubes with the aim to separate the PMN; the purified PMN culture was cultured for 24h with LPS and TNF alpha. In the cell-free supernatants the induction of PMN interleukin 8 (IL8), interleukin 18 (IL18), and TNF alpha were measured.

Results: The expression of IL8 were significantly higher in PMN of SAPHO compared to PsA and HC: 2712.3 vs. 1742.9 vs. 1268.0 pg/ml (p=0.018). Expression of TNF alpha and IL18 did not differ between the two entities. Two out of four SAPHO patients developed clinical response to treatment with secukinumab measured by clinical scoring markers; the corresponding expression of IL8 in PMN were significantly reduced by secukinumab treatment: 3781.7 vs. 882.0 pg/ml (p=0.010). In contrast, the SAPHO patients without response to secukinumab treatment showed lower IL8 expression prior to secukinumab and no decrease of IL 8 expression after secukinumab treatment: 1981.3 vs. 1611.8 pg/ml. All PsA patients did not developed changes in IL8 expression due to secukinumab treatment independent from treatment response: 1742.9 vs. 1554.4.

Conclusion: In SAPHO patients the interleukin 8 expression in PMN could be discussed as prognostic marker for disease activity and possible secukinumab treatment response. However, the observation has to be confirmed in prospective studies of larger cohorts of SAPHO patients.


References

1.
Hurtado-Nedelec M, Chollet-Martin S, Nicaise-Roland P, Grootenboer-Mignot S, Ruimy R, Meyer O, Hayem G. Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Rheumatology (Oxford). 2008 Aug;47(8):1160-7. DOI: 10.1093/rheumatology/ken185 Externer Link
2.
Firinu D, Barca MP, Lorrai MM, Perra S, Cabras S, Muggianu E, Di Martino ML, Manconi PE, Del Giacco SR. TH17 cells are increased in the peripheral blood of patients with SAPHO syndrome. Autoimmunity. 2014 Sep;47(6):389-94. DOI: 10.3109/08916934.2014.906582 Externer Link