Pos0875 autoantibodies Directed to G-Protein Coupled Receptors Correlate With Disease Activity Scores in Patients With Psoriatic Arthritis

Abstract

BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory disease that affects the skin, nails, tendons and joints. In addition, several comorbidities have been identified with PsA. In particular, a frequent occurrence of fatigue and mental disorders such as depression have been described in patients with PsA. Key cellular players in pathophysiology of PsA are T cells. However, in recent years, various autoantibodies such as anti-LL37 and anti-Pso-p27 have been identified in PsA as well [1]. Autoantibodies targeting G protein-coupled receptors (GPCRs) have been identified in several diseases and are involved in disease pathophysiology [2]. Many of these autoantibodies are agonists that enhance the effect of the natural ligand at the receptor [3].ObjectivesThe aim of this study was to investigate the association between autoantibodies directed to distinct GPCRs and disease activity as well as comorbidities in PsA.MethodsIn a prospective observational study forty-five patients with an active PsA according to CASPAR criteria and 24 healthy controls (HCs) matched according to age and sex were included in this study. The serum-concentrations of 20 autoantibodies directed to GPCRs involved in the renin-angiotensin-aldosterone system, the sympathetic and parasympathetic nervous system as well as chemokine, complement and scavenger receptors, were measured by the company CellTrend GmbH (Luckenwalde, Germany). Autoantibodies measured in patient’s sera at baseline were transformed and adjusted for age as confounder for further analyses. To compare autoantibody concentrations between PsA and HCs we applied Two-Way-ANOVA. Correlation analyses were performed using Pearson correlation. Autoantibody concentrations between patients with and without depression were analyzed by Student’s T test and binary logistic regression.ResultsPatients were equally distributed according to sex (male 51.1%, female 48.9%) and of a mean age of 47.5 ± 13.2 years. Mean arthritic disease manifestation assessed by DAPSA was 44.4 ± 21.2. Patients displayed a disease activity with a mean PASI of 6.19 ± 6.33, and high impact on patient reported outcomes with a mean DLQI of 10.3 ± 7.4 and a mean HAQ of 1.0 ± 0.8. Autoantibody concentrations did not differ significantly between patients with PsA and HCs. Further analysis revealed significant correlations between autoantibody levels, disease activity scores and treatment response of cutaneous disease manifestation after 16 weeks of treatment (Δ PASI),Figure 1. Moreover, the levels autoantibodies directed to the MAS receptor, CXCR3, PAR1 and stabilin were significantly higher in patients with PsA suffering from depression compared to patients without depression (MASR: p=0.035; CXCR3: p=0.011; PAR1: p=0.047; stabilin: p=0.035), although binary logistic regression did not prove any predictive value for these four antibodies.ConclusionAutoantibodies directed to GPCRs correlated with disease activity scores in patients with PsA. Further larger analyses regarding the functional role of these autoantibodies in PsA are required.References[1]Koussiouris J, Chandran V. Autoantibodies in Psoriatic Disease. The Journal of Applied Laboratory Medicine (2022) 7:281–293. doi: 10.1093/jalm/jfab120[2]Skiba MA, Kruse AC. Autoantibodies as Endogenous Modulators of GPCR Signaling. Trends in Pharmacological Sciences (2021) 42:135–150. doi: 10.1016/j.tips.2020.11.013[3]Yue X, Yin J, Wang X, Heidecke H, Hackel AM, Dong X, Kasper B, Wen L, Zhang L, Schulze-Forster K, et al. Induced antibodies directed to the angiotensin receptor type 1 provoke skin and lung inflammation, dermal fibrosis and act species overarching. Ann Rheum Dis (2022)annrheumdis-2021-222088. doi: 10.1136/annrheumdis-2021-222088Figure 1.Heatmap displaying Pearson’s correlation coefficient of correlation analyses between diseases activity scores and autoantibody concentrations adjusted for age at baseline. Pearson correlation analyses with a p-value <0.05 are marked with a box.Acknowledgements:NIL.Disclosure of InterestsHanna Grasshoff Speakers bureau: Abbvie, Sara Comduehr: None declared, Justus Ohmes: None declared, Diamant Thaçi Speakers bureau: Diamant Thaçi has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB., Consultant of: Diamant Thaçi has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB, Kai Schulze-Forster Shareholder of: board of management: CellTrend, Harald Heidecke Shareholder of: board of management: CellTrend, Peter Lamprecht: None declared, Gabriela Riemekasten: None declare.d.