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.
- arthritis, psoriatic
Data availability statement
Data are available on reasonable request.
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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.
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