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Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+ CD161+ CD4+ T helper cells in psoriatic arthritis joints

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Abstract

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-F+CD161+IL23+ CD4+ T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-F+IL23+ - IL17A-F+CD161+ - and IL17A-F+CD161+IL23+ CD4+ T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4+T and CD4+IL23+ T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA.

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Acknowledgements

This work was supported by grants from the Italian Ministry of Education, University and Research (MIUR-2009EE3SWA; FIRB 2011).

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Ugo Fiocco, Mara Felicetti, Anna Scanu, Francesca Oliviero, Bernd Raffeiner, Maristella Vezzù, Leonardo Punzi & Andrea Doria

  2. Section of Radiology, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Roberto Stramare, Alessandro Coran & Leopoldo Rubaltelli

  3. Haematology and Clinical Immunology Branch, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Veronica Martini

  4. Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via S. Pansini 5, 80131, Naples, Italy

    Francesco Caso, Luisa Costa & Raffaele Scarpa

  5. Department of Information Engineering, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Gaia Rizzo, Matteo Tonietto & Enrico Grisan

  6. Department of Cardiac, Thoracic and Vascular Sciences - Section of Anatomy Pathology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Francesca Lunardi

  7. Department of Medicine, Unit of Ultrasonography in Internal Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    David Sacerdoti

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  1. Ugo Fiocco
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Correspondence to Ugo Fiocco.

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The study was approved by the local ethic committee of the University Hospital of Padova (Italy) (number 52723; October 11, 2010).

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Fiocco, U., Stramare, R., Martini, V. et al. Quantitative imaging by pixel-based contrast-enhanced ultrasound reveals a linear relationship between synovial vascular perfusion and the recruitment of pathogenic IL-17A-F+IL-23+ CD161+ CD4+ T helper cells in psoriatic arthritis joints. Clin Rheumatol 36, 391–399 (2017). https://doi.org/10.1007/s10067-016-3500-x

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