SAT0359 THE ASSOCIATION BETWEEN IMAGING SUB-PHENOTYPES OF PSORIATIC ARTHRITIS AND GENE EXPRESSION PROFILES
Authors: L. Eder, Q. Li, S. Rahmati, I. Eshed, P. Rahman, I. Jurisica, V. Chandran
Journal: Annals of the Rheumatic Diseases (2020)

Background: Heterogeneity is a hallmark of psoriatic arthritis (PsA), which is reflected in diverse clinical, imaging and molecular features that may reflect disease course and response to treatment. We hypothesized that specific molecular pathways underlie the various manifestations of PsA. Objectives: To create a model for accurate and biologically meaningful sub-phenotyping of PsA using imaging and molecular data. Specifically, we aimed to identify imaging sub-phenotypes in patients with PsA and determine their association with whole blood mRNA expression markers. Methods: 55 patients with PsA ready to initiate treatment for active disease were prospectively recruited. An ultrasound assessment of the extent of musculoskeletal inflammation in 64 joints, 34 tendons and 16 entheses was performed. Sonographic inflammation (in greyscale and Doppler) of the following domains was graded for: a) synovitis; b) peri-tendonitis; c) tenosynovitis; and d) enthesitis. A global inflammatory score was calculated for each tissue domain. Peripheral blood was profiled with RNAseq, and gene expression data were obtained. Analyses were performed in two stages: 1) Unsupervised cluster analysis was performed using hierarchial and k-means to define imaging sub-phenotypes in PsA that reflected the predominant tissue involved; 2) Principal component analysis with ellipses was used to determine the association between imaging-defined clusters and peripheral blood gene expression profile. Results: The patients could be divided into 3 groups based on unsupervised hierarchical and k-means clustering of images indicating the predominant involved tissue (Figure 1): 1) Enthesitis predominant (N=13 [24%]); 2) Peri-tendonitis predominant (N=11 [20%]); 3); Synovitis predominant (N=31 [56%]). Patients in the synovitis predominant group had more nail involvement, while those in the peri-tendonitis group had the highest number of clinically active joints (Table 1). Unsupervised clustering of gene expression data identified three clusters that partially overlapped with the imaging clustering (Figure 2). Overall, 344 genes were differentially expressed (p&lt;0.05) in two of the three comparisons between the imaging clusters. Table 1. Clinical Features by Imaging Clustering Variable Enthesitis predominant cluster (N=13 ) Peritendonitis predominant cluster (N=11 ) Synovitis predominant cluster (N=31 ) Age (years) 47 (14) 49 (16) 45 (20) Sex: Female 8 (61.5%) 5 (45.5%) 15 (48.4%) PsA duration (years) 1.2 (1.5) 1.6 (11.5) 0.8 (3.7) BMI 29.4 (6.8) 25 (8.1) 26.1 (8.4) Nail lesions 3 (23.1% ) 5 (45.5% ) 17 (54.8% ) PASI 1.2 (2.7) 1.2 (3.2) 2.8 (7.8) Tender joint count 6 (9 ) 11 (5 ) 3 (6 ) Swollen joint count 2 (6 ) 10 (7 ) 3 (6 ) Dactylitis 3 (23.1%) 4 (36.4%) 7 (22.6%) Enthesitis count 3 (3 ) 1 (4 ) 0 (2 ) Enthesitis 12 (92.3% ) 7 (63.6% ) 15 (48.4% ) hsCRP 2.9 (8.8) 8.5 (21.5) 3.6 (9.4) Median (IQ range) and frequencies (%) Bolded=Statistically different between the 3 groups (p&lt;0.05) Conclusion: We identified three different imaging clusters based on the predominant tissue involved in patients with active PsA. Distinct gene expression profiles may underlie these imaging clusters seen in PsA. Acknowledgments: The study was supported by a Discovery Grant from the National Psoriasis Foundation. Disclosure of Interests: Lihi Eder Grant/research support from: Abbvie, Lily, Janssen, Amgen, Novartis, Consultant of: Janssen, Speakers bureau: Abbvie, Lily, Janssen, Amgen, Novartis, Quan Li: None declared, Sara Rahmati: None declared, Iris Eshed: None declared, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Igor Jurisica Grant/research support from: IBM, Vinod Chandran Grant/research support from: Abbvie, Celgene, Consultant of: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lily, Janssen, Novartis, Pfizer, UCB, Employee of: Spouse employed by Eli Lily