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Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients

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Abstract

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

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Acknowledgements

This work was supported by intramural grants from the University of Catania, Italy.

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Authors and Affiliations

  1. Department of Biomedical and Biotechnological Sciences, University of Catania, via Santa Sofia 97, 95123, Catania, Italy

    F. D’Amico, M. Granata, E. Skarmoutsou, C. Trovato, G. Lovero & M. C. Mazzarino

  2. Servizio di Anatomia Patologica, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy

    P. Gangemi

  3. Unità Operativa Complessa di Dermatologia, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy

    V. Longo & M. Pettinato

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  1. F. D’Amico
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  2. M. Granata
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Correspondence to F. D’Amico.

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D’Amico, F., Granata, M., Skarmoutsou, E. et al. Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients. Inflamm. Res. 67, 609–616 (2018). https://doi.org/10.1007/s00011-018-1147-6

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  • DOI: https://doi.org/10.1007/s00011-018-1147-6

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