16 PsA pathogenetic studies Basic Science Session 2. Recent Advances in Our Understanding of Psoriatic Arthritis Pathogenesis Erik Lubberts 1 , Jose U. Scher 2 , and Oliver FitzGerald 3  ABSTRACT. e second basic science session at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting focused on 2 recent publications that have increased our understanding of the pathogenesis of psoriatic arthritis (PsA). Data from the first publication, presented by Prof. Erik Lubberts, showed that interleukin (IL)-17A is produced by CD4+ and not CD8+ T cells in PsA synovial fluid fol- lowing T cell receptor activation. ese findings contrast with previously published data, which had sug- gested that CD8+ T cells are a prominent source of IL-17A. In further experiments, they showed that when CD8+ T cells were stimulated with paramethoxyamphetamine/ionomycin, relatively high levels of IL-17A were detected. Prof. Jose Scher presented work on the role of the microbiome in PsA and more specifically, on pharmacomicrobiomics. He demonstrated the baseline collection of genomes and genes from the micro- biota community (the metagenome) can be used as predictor for future treatment response in early rheuma- toid arthritis and also likely in PsA. Key Indexing Terms: GRAPPA, psoriasis, psoriatic arthritis As part of the supplement series GRAPPA 2021, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. 1 E. Lubberts, PhD, Erasmus University Medical Center, University Medical Center, Rotterdam, the Netherlands; 2 J.U. Scher, MD, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA; 3 O. FitzGerald, MD, FRCPI, FRCP(UK), Consultant Rheumatologist, Newman Clinical Research Professor, Conway Institute for Biomolecular Research, University College Dublin, Dublin, Ireland. OF has received research grants and/or consulting fees from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. JUS has received research grants and/or consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB. EL has received research grants and/or consulting fees from Novartis, Eli Lilly, and Janssen. This paper does not require institutional review board approval. Address correspondence to Prof. O. FitzGerald, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Email: oliver.fitzgerald@ucd.ie. Accepted for publication December 7, 2021. Introduction Significant advances have been made in recent years to our understanding of the pathogenesis of psoriatic arthritis (PsA). Studies have suggested an important role for CD8+ T cells, which produce interleukin (IL)-17A, with a population of such cells identified in PsA synovial fluid. 1 is observation is consis- tent with other known PsA findings including the association of PsA with HLA class 1 antigens, which present antigen to CD8+ T cells. e work of Prof. Erik Lubberts and his colleagues, presented below, casts some doubt on the importance of CD8+ T cells, as CD4+ and not CD8+ T cells produced IL-17A following T cell receptor (TCR) activation. However, the rela- tive roles of CD4+ and CD8+ T cells in PsA pathogenesis require further elucidation. Potentially connecting the gut with stimulating the expansion of IL-17A–producing T cells are changes in the gut microbiome. Prof. Jose Scher recently published several important papers on this topic, which he included in his review of the current under- standing of changes in gut microbiome, both in disease patho- genesis and also in determining treatment responses. is is an exciting area of research that deserves much greater attention. Basic research presentations Basic research presentation by Prof. Lubberts on the role of CD4+ cells. IL-17A was found to be produced by CD4+ but not CD8+ T cells in synovial fluid following TCR activation and to regulate different inflammatory mediators compared to tumor necrosis factor (TNF) in a model of PsA synovitis. is research was discussed by Prof. Lubberts on behalf of his colleagues at Erasmus University Medical Center (Erasmus MC): X. Xu, N. Davelaar, A.M.C. Otten-Mus, P.S. Asmawidjaja, J.M.W. Hazes, D.L.P. Baeten, M. Vis, R. Bisoendial and E.P. Prens. An increased percentage of IL-17A–producing T cells, including CD4+ and CD8+ T cells, have been found in patients with PsA and correlates with PsA disease activity. 1,2 Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared with patients with psoriasis (PsO) alone. 3 However, whether the synovial fluid–derived CD8+ T cells also excrete IL-17A is not clear. In their work, Prof. Lubberts and his team presented and confirmed enriched percentage of IL-17A+CD8+ T cells in PsA synovial fluid compared to peripheral blood using flow cytom- etry techniques. 1 Using this technique, the cells are stimulated for 4–6 hours with paramethoxyamphetamine (PMA)/iono- mycin. Interestingly, when FACS-sorted synovial fluid–derived CD4+ or CD8+ T cells were cultured and stimulated with anti-CD3/anti-CD28 for 72 hours, CD4+ (but not CD8+) e Journal of Rheumatology 2022;49 Suppl 1:16–9 doi:10.3899/jrheum.211321 First Release February 15 2022 © 2022 e Journal of Rheumatology www.jrheum.org Downloaded on November 8, 2024 from