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Concise report: a minimal-invasive method to retrieve and identify entheseal tissue from psoriatic arthritis patients
  1. Milena L Pachowsky1,2,
  2. Maria Gabriella Raimondo1,2,
  3. Cong Xu1,2,
  4. Simon Rauber1,2,
  5. Koray Tascilar1,2,
  6. Hannah Labinsky1,2,
  7. Mario Vogg1,2,
  8. Mina Saad Aziz Saad1,2,
  9. David Simon1,2,
  10. Juergen Rech1,2,
  11. Alina Soare1,2,
  12. Lars Braeuer3,
  13. Arnd Kleyer1,2,
  14. Georg Schett1,2,
  15. Andreas Ramming1,2
  1. 1Department of Internal Medicine 3, Rheumatology & Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nurnberg and Universitatsklinikum Erlangen, Erlangen, Bayern, Germany
  2. 2Deutsches Zentrum Immuntherapie, Friedrich-Alexander-University (FAU) Erlangen-Nurnberg and Universitatsklinikum Erlangen, Erlangen, Germany
  3. 3Institute of Anatomy, Chair II, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
  1. Correspondence to Dr Andreas Ramming, University Hospital Erlangen, Department of Internal Medicine 3, Rheumatology & Immunology, Friedrich-Alexander-Universitat Erlangen-Nurnberg Medizinische Fakultat, Erlangen, Bayern, Germany; Andreas.ramming{at}uk-erlangen.de

Abstract

Objectives To establish a minimally invasive biopsy technique for the analysis of entheseal tissue in patients with psoriatic arthritis (PsA).

Methods Human cadavers were used for establishing the technique to retrieve tissue from the lateral humeral epicondyle enthesis (cadaveric biopsies). After biopsy, the entire enthesis was surgically resected (cadaveric resections). Biopsies and resections were assessed by label-free second harmonic generation (SHG) microscopy. The same technique was then applied in patients with PsA with definition of entheseal tissue by SHG, staining of CD45+immune cells and RNA extraction.

Results Entheseal biopsies from five cadavers allowed the retrieval of entheseal tissue as validated by the analysis of resection material. Microscopy of biopsy and resection sections allowed differentiation of entheseal, tendon and muscle tissue by SHG and definition of specific intensity thresholds for entheseal tissue. In subsequent entheseal biopsies of 10 PsA patients: the fraction of entheseal tissue was high (65%) and comparable to cadaveric biopsies (68%) as assessed by SHG microscopy. Furthermore, PsA biopsies showed immune cell infiltration and sufficient retrieval of RNA for further molecular analysis.

Conclusion Entheseal biopsy of the lateral epicondyle is feasible in patients with PsA allowing reliable retrieval of entheseal tissue and its identification by SHG microscopy.

  • inflammation
  • arthritis, psoriatic
  • ultrasonography

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Handling editor Josef S Smolen

  • MLP, MGR and CX contributed equally.

  • Contributors MLP, MGR, CX, GS and AR designed the study; MLP, MGR, CX, SR, KT, HL, MV, MSAS, DS, JR, AS, LB, AK, AR acquired data; MLP, MGR, CX, SR, KT, AS, LB, GS and AR interpreted data; MLP, DS, JR, LB, AK provided materials; MLP, MGR, CX, GS and AR prepared the manuscript. Author acting as guarantor: AR.

  • Funding The work was supported by the Deutsche Forschungsgemeinschaft (RA 2506/4-1, RA 2506/4-2, RA 2506/6-1 to AR; SO 1735/2-1 to AS, SCHE 1583/7-1 to GS; and CRC1181 to GS and AR [project C06]), European Research Council (853508 BARRIER BREAK) to AR, EC project Nanoscope 4D to GS, the Innovative Medicine Initiative (IMI; project HIPPOCRATES to DS and GS), Bundesministerium für Bildung und Forschung (MASCARA to GS and AR), the Interdisciplinary Centre for Clinical Research, Erlangen (F4-48 to AR), the ELAN Fonds of the Universitätsklinikum Erlangen (19-02-18-1 to MGR), Else Kröner-Memorial Scholarship (DS, no. 2019_EKMS.27), PARTNER Fellowship Program dedicated to MGR, Emerging Fields Initiative (EFI) of the FAU and the STAEDTLER Stiftung (EFI_Verbund_Med_05_MIRACLE) to MLP and AK, and Novartis Pharma GmbH.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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