POS1063 STAT PHOSPHORYLATION AS A MARKER FOR DISEASE ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: AN EXPLORATIVE ANALYSIS

Abstract

Background Numerous cytokines that influence disease activity in psoriatic arthritis (PsA) are modulators of the Janus Kinases/Signal Transducers and Activators of Transcription (JAK/STAT) pathway. The JAK1/STAT1/STAT3/STAT5 network can drive the expansion of Th17 and regulatory T cells via proinflammatory cytokines in PsA joints,[1], [2] while hyperphosphorylation of STAT3 in immune cells has previously been shown to promote PsA pathogenesis through the Interleukin (IL)-23/IL-17/IL-22 axis.[3] Therefore, the phosphorylation status of STAT molecules in leucocytes of PsA patients may indicate active disease and could potentially guide treatment with JAK inhibitors. Objectives To analyse phosphorylated STAT (pSTAT) levels of circulating leucocyte subsets in PsA patients with active and inactive disease Methods Whole blood was drawn on consecutive PsA patients fulfilling the CASPAR criteria[4] to perform flow cytometry analysis using the BD FACSLyric platform. Disease activity was assessed using the Disease activity for psoriasis arthritis (DAPSA) score.[5] All steps from storage of drawn blood to cell fixation were performed at 4°C to prevent auto-activation of leucocytes. The geometric mean fluorescence intensities (gMFI) of pSTATs in granulocytes, monocytes, B cells and CD4+/- naïve/memory T cells were compared between patients with moderate to high (MoDA/HDA) and remission to low disease activity (REM/LDA). Correlation analysis between gMFIs and DAPSA scores were performed. Results Forty-two patients (female ratio: 0.48) with established PsA (median ± standard deviation, age: 56 ± 12.54 years, disease duration: 8.50 ± 7.10 years) were included in this study. Twenty-one percent of patients were in MoDA/HDA, while the remaining 79% were in REM/LDA. Patients in MoDA/HDA showed significantly higher pSTAT3 levels in CD4+ naïve (gMFI median ± standard deviation: 284.5 ± 79.9 vs 238 ± 92.9, p = 0.011), CD4- naïve (297 ± 107.5 vs 238 ± 98.4, p = 0.04), CD4+ memory (227 ± 62.9 vs 190.5 ± 72.2, p = 0.009) and CD4- memory T cells (209 ± 66.8 vs 167.0 ± 64.9, p = 0.036). On the other hand, PsA patients in remission or low disease activity displayed higher pSTAT1 levels in granulocytes (2509 ± 1887 vs 1330.5 ± 784.1, p = 0.040) and monocytes (255 ± 230 vs 144 ± 62.5, p = 0.049). Positive correlations were found between DAPSA scores and pSTAT3 in CD4+ naïve and memory T cells (Spearman’s correlation coefficient rho (ρ) = 0.5, p = 0.0012 and ρ = 0.47, p = 0.0025 resp.) whereas pSTAT1 in granulocytes and monocytes were negatively correlated with the DAPSA scores (ρ = -0.45, p = 0.0074 and ρ = -0.34, p = 0.05). Conclusion Differential phosphorylation of STAT3 and STAT1 molecules in circulating leucocyte subsets indicates PsA disease activity. Further studies to examine the value of STAT phosphorylation patterns guiding JAK inhibitor therapy are underway. References [1]U. Fiocco et al., “Ex vivo signaling protein mapping in T lymphocytes in the psoriatic arthritis joints,” J. Rheumatol., vol. 93, pp. 48–52, 2015, doi: 10.3899/jrheum.150636. [2]S. K. Raychaudhuri, C. Abria, and S. P. Raychaudhuri, “Regulatory role of the JAK STAT kinase signalling system on the IL-23/IL-17 cytokine axis in psoriatic arthritis,” Ann. Rheum. Dis., vol. 76, no. 10, pp. e36–e36, 2017. [3]E. Calautti, L. Avalle, and V. Poli, “Psoriasis: A STAT3-centric view,” International Journal of Molecular Sciences, vol. 19, no. 1. MDPI AG, Jan. 06, 2018, doi: 10.3390/ijms19010171. [4]W. Taylor, D. Gladman, P. Helliwell, A. Marchesoni, P. Mease, and H. Mielants, “Classification criteria for psoriatic arthritis: Development of new criteria from a large international study,” Arthritis Rheum., vol. 54, no. 8, pp. 2665–2673, 2006, doi: 10.1002/art.21972. [5]M. M. Schoels, D. Aletaha, F. Alasti, and J. S. Smolen, “Disease activity in psoriatic arthritis (PsA): Defining remission and treatment success using the DAPSA score,” Ann. Rheum. Dis., vol. 75, no. 5, pp. 811–818, 2016, doi: 10.1136/annrheumdis-2015-207507. Disclosure of Interests Barbara Dreo: None declared, Daniel Ruben Pietsch: None declared, Rusmir Husic Speakers bureau: MSD, Lilly und Abbvie, Angelika Lackner: None declared, Johannes Fessler: None declared, Janine Rupp: None declared, Anirudh Subramanian Muralikrishnan: None declared, Jens Thiel Speakers bureau: GSK, BMS, AbbVie, Novartis, Consultant of: GSK, Novartis, Grant/research support from: BMS, Martin Stradner Speakers bureau: Eli Lilly, Pfizer, MSD, BMS, AbbVie, Janssen, Consultant of: Eli Lilly, AbbVie, Janssen, Philipp Bosch Grant/research support from: Pfizer