You are here

Article Text

Article menu

Download PDFPDF

Scientific Abstracts
Oral Abstract Presentations
Clinical Abstract Sessions: SpA & PsA - Treatment effects and response prediction
OP0161 MULTI-MODAL ANALYSIS OF SYNOVIAL TISSUE INFLAMMATION INFORMS ON TREATMENT RESPONSE IN ACTIVE PSORIATIC ARTHRITIS
  1. D. Bruno1,2,3,
  2. D. Somma4,
  3. L. A. Coletto4,
  4. B. Tolusso2,
  5. C. DI Mario2,
  6. S. Perniola2,3,
  7. V. Varriano3,
  8. A. Paglionico3,
  9. M. Gessi5,
  10. R. Benvenuto5,
  11. L. Bui5,
  12. L. Petricca6,
  13. M. R. Gigante6,
  14. L. Macdonald4,
  15. A. Elmesmari4,
  16. G. Peluso6,
  17. M. M. Lizzio6,
  18. M. A. D’ Agostino6,
  19. E. Gremese2,3,4,
  20. M. Kurowska-Stolarska4,
  21. S. Alivernini2,4,6
  1. 1University of Verona, Verona, Italy
  2. 2Immunology Research Core Facility – Gemelli Science and Technology Park (GSTeP) - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  3. 3Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  4. 4Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, Glasgow, United Kingdom
  5. 5Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  6. 6Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

Abstract

Background: Ultrasound (US)-guided Synovial Tissue (ST) biopsy has emerged as a safe procedure for translational research into inflammatory arthritis. The histological and molecular analysis of ST heterogeneity have a prospect to unravel the extreme clinical complexity of the disease pathotypes and to inform treatment strategies.

Objectives: To carry out a multi-modal assessment of heterogeneity of ST obtained through US-guided biopsies from patients with Psoriatic Arthritis (PsA), across different disease phases.

Methods: 397 patients fulfilling the CASPAR criteria[1] for PsA underwent US-guided ST biopsy. At baseline, patients were categorized based on their disease phase: n=210 naïve to csDMARDs; n=131 resistant to cs/b-DMARDs and n=56 in sustained clinical and US remission or in low disease activity (Rem/LDA) state based on DAPSA score[2]. All ST specimens were processed for H&E-based semiquantitative synovitis quantification (KSS)[3], implemented with the pathotype assessment[4].Each naive to treatment PsA was treated according to the EULAR/GRAPPA[5,6] recommendations and DAPSA Rem/LDA rate at 6 months was recorded. In addition, ST from n=18 patients, representing all disease phases, were digested and alive cells were sorted using FACS-ARIA III and single-cell RNA sequencing (scRNAseq) conducted using 10x Genomics (Chemistry 3′ v3.1, Illumina HiSeq 4000, with depth of 20,000 reads/cell).

Results: The distribution of KSS was significantly different across the different PsA phases (ANOVA p<0.001). KSS was significantly higher in cs/b-DMARDs resistant patients than naive PsA(p<0.0001) and PsA in remission/LDA (p<0.0001). Regardless of the disease phase, KSS directly correlated with disease activity in terms of DAPSA (r=0.476, p<0.001). Evaluation of cellular composition showed that naive and cs/b-DMARDs resistant PsA had similar rates of diffuse-myeloid (DM) pathotype (47,2% and 45%, p=0.69. However, cs/b-DMARDs resistant PsA exhibited higher rate of lympho-myeloid (LM) pathotype than naïve (p=0,002). Among naïve PsA patients, KSS was significantly higher in those with concomitant dactylitis (p<0.001) and skin (p=0.04) and nail disease (p<0.001). Moreover, those who achieved Rem/LDA at 6 months showed, at baseline, significantly lower KSS compared to those not achieving this clinical outcome (p<0.001). In single cell analysis, we obtained transcriptomic profiles for 174,672 synovial tissue-derived cells from which, 17,932 myeloid cells were computationally isolated based on the expression of CD14, CD163, MARCO, LYZ, CD11b and CD64. We identified 9 different myeloid subclusters: 2 clusters of lining layer synovial tissue macrophages (STMs) based on the expression of MerTKposTREM2posTIMD4pos and MerTKposTREM2lowTIMD4low respectively, 5 clusters of sublining layer STMs (MerTKposFOLR2posLYVE1pos, MerTKposFOLR2posLYVE1posICAM1pos, MerTKnegS100A12pos, MerTKnegISG15posSLAMF7pos, CLEC10Apos) and 2 clusters of dendritic cells (DCs) (CD1cposCLEC10Apos DC2, CD1cnegCLEC10Apos iDC3). Each of these clusters was present across all disease phases but differed in relative proportions. Specifically, ST of naive PsA with LM pathotype was enriched with sublining MerTKnegS100A12pos STMs as compared to naive PsA with DM pathotype. ST of cs/b-DMARDs resistant PsA with DM pathotype showed an expansion of sublining MerTKnegS100A12pos and MerTKnegISG15posSLAMF7pos STMs compared to the same disease state with pauci-immune (PI) pathotype. Finally, ST of naive and cs/b-DMARDs resistant PsA showed an enrichment of CD1cnegCLEC10apos/iDC3, both in patients with LM and DM pathotypes, compared to the same disease state with PI pathotype.

Conclusion: KSS is a reliable tool for synovitis assessment in PsA, being related to clinical outcome. Transcriptomic analysis revealed that distinct STM and DC clusters contribute to different pathotypes of naive and resistant to treatment PsA.

REFERENCES: [1] Taylor W, et al. Arthritis Rheum. 2006.

[2] Schoels M, et al. Ann Rheum Dis. 2010.

[3] Krenn V, et al. Histopathology. 2006.

[4] Alivernini S, et al. Arthritis Rheumatol. 2021.

[5] Gossec L, et al. Ann Rheum Dis. 2020.

[6] Coates LC, et al. J Rheumatol. 2022.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

  • -omics
  • Synovium

https://doi.org/10.1136/annrheumdis-2024-eular.4868

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.