Multi-omics Diagnosis of Psoriatic Arthritis

Journal of Psoriasis and Psoriatic Arthritis 2022, Vol. 7(2) 99–108 © The Author(s) 2022 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/24755303221084594 journals.sagepub.com/home/jps Abstracts from the 2021 NPF Research Symposium Meeting Every 2 years the National Psoriasis Foundation hosts the Research Symposium, where the latest in psoriatic disease and comorbidities research is presented and discussed. The 2021 symposium focused on research efforts aimed at improving health outcomes in those with psoriatic disease. NPF welcomed stakeholders to submit abstracts that are related to outcomes in psoriasis and psoriatic arthritis. Via peer-review, 19 abstracts were accepted and provided permission to share here. Multi-omics Diagnosis of Psoriatic Arthritis Julie Hong, Mimi Chung, Jared Liu, Sugandh Kumar, ZhiMing Huang, Diana Paez, Megan Mosca, Edward Hadeler, Marwa Hakimi, Samuel Yeroushalmi, Erin Bartholomew, Chun Ye, Mehrdad Matloubian, Tina Bhutani, Lianne Gensler, and Wilson Liao University of California, San Francisco, CA, USA Up to 30% of patients with psoriasis also develop psoriatic arthritis (PsA), a debilitating condition affecting the joints and musculoskeletal system that significantly lowers patients’ quality of life. It is crucial to have a diagnostic test available for PsA, which will allow for earlier detection and therapeutic intervention. To tackle this problem, we brought together a diverse team of dermatologists, rheumatologists, and bioinformaticians. We hypothesized that to identify suitable molecular markers for PsA, we would need to take a discovery approach casting a broad net in search of novel markers. We therefore utilized CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) and SNP genotyping to profile the PBMCs of patients with PsA, psoriasis without PsA (PsO), and healthy controls. We generated full single cell transcriptome and 282-cell surface marker data for 90 individuals, identifying over 30 distinct PBMC subsets including CD4 CTL, CD4 Naive, CD4 Proliferating, CD4 TCM, CD4 TEM, CD8 Naive, C08 Proliferating, CD8 TCM, CD8 TEM, Treg, gamma delta T, B intermediate, B memory, B naive, Plasmablast, ILC, MAIT, NK, NK Proliferating, NK CD56bright, C014 Mono, CD16 Mono, cDC1, cOC2, pDC, ASDC, and HSPC. Comparing PsA with PsO, we found that the cellular proportion of Tregs significantly differed between these two groups. Moreover, we identified >1000 individual gene or protein markers differentially expressed between PsA and PsO with an adjusted P-value less than 1E-04. We constructed a multi-marker predictive model demonstrating a mean PsA classification accuracy of >95%. In the next phase of this project, wewill validate the PsA signature using independent patient cohorts. Ultimately, we hope to develop a diagnostic test that is simple for patients to obtain, that can be objectively interpreted, and is highly accurate. Cardiac biomarkers are associated with the development of cardiovascular events in patients with psoriatic disease Keith Colaco, Ker-Ai Lee, Shadi Akhtari, Raz Winer, Paul Welsh, Naveed Sattar, Iain B McInnes, Vinod Chandran, Paula Harvey, Richard J Cook, Dafna D Gladman, Vincent Piguet, and Lihi Eder Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada Department of Cardiology, Women’s College Hospital, Toronto, ON, Canada Department of Medicine, University of Toronto, Toronto, ON, Canada Department of Neurology, Rambam Health Care Campus, Haifa, Israel BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada Background/Purpose: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and troponin I (Tnl) are established cardiac biomarkers that predict cardiovascular events (CVEs) and mortality in apparently healthy individuals and at-risk populations. While patients with psoriatic arthritis and psoriasis, collectively termed psoriatic disease (PsD), have an increased risk of developing CVEs, the use of these cardiac biomarkers to predict CV risk has not been investigated in this population. We aimed to evaluate the association between these cardiac biomarkers and incident CVEs and assess their predictive value beyond the Framingham Risk Score (FRS). Methods: A longitudinal cohort study was conducted in patients with PsD without prior history of CVEs. NT-proBNP and Tnl concentrations were measured using automated clinical assays in the first available serum sample. The study outcome included any of the following CVEs occurring within the first 10 years of biomarker assessment: angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, revascularization procedures and CV death. Associations with incident CVEs were analyzed separately for each biomarker using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for the FRS. The added value of cardiac biomarkers to improve predictive performance beyond the FRS was assessed using the area under the receiver operator characteristic curve (AUC), net reclassification index (NRI) and integrated discrimination index (IOI). Results: A total of 1000 patients with PsD were assessed between 2002 and 2019 (mean age 49 ± 12.8 years, 44.6% female). During a mean follow-up of 7.1 years, 64 (6.4%) patients developed incident CVEs. Both Tnl (Hazard Ratio (HR) 3.02, 95% Confidence Interval (Cl) 1.12, 8.16) and NTproBNP (HR2.02; 95% Cl 1.28, 3.18) predicted CVEs independently of the FRS. The association was stronger in males than females. Including all cardiac biomarkers and the FRS in a single model, NTproBNP retained statistical significance (HR 1.91, 95% Cl 1.23, 2.97), while Tnl did not (HR 2.60, 95% Cl .98, 6.87). When comparing the predictive performance of the base model (FRS alone, AUC 75.4) to the expanded models, there was no significant improvement in any of the predictive indices with the addition of Tnl (AUC 73.5, P = .21; NRI .08, P = .67; IOI .005, P = .37), NTproBNP (AUC 71.0, P =.35; NRI .20, P = .06; IOI .017, P = .10), or both Tnl and NT-proBNP (AUC 7.0, P = .23; NRI .27, P = .05; IOI .021, p =.05). Conclusions: In patients with PsO, elevated NT-proBNP and Tnl predict incident CVEs independent of the FRS. We did not observe a significant improvement in the performance of the predictive model when combining these cardiac biomarkers with the FRS. MHC haplotype controls the development of IL-23 minicircle-induced murine spondyloarthritis Emma K. Haley, Mederbek Matmusaev, Jyotsna Soundararajan, and Joerg Ermann Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital Boston, MA, USA Harvard Medical School, Boston, MA, USA Introduction: Arthritis induced by systemic overexpression of IL-23 in B1.RIII mice is an established model of spondyloarthritis. Tissue-resident gd T cells expressing the IL-23 receptor are thought to play a critical role in this model. B1.RIII is an MHC congenic strain carrying the RIII-derived H-2r region on a C57BL/10 (B10) background. We found that neither B10 nor the closely related C57BL/6 (B6) reference strain develop IL-23 minicircle-induced arthritis. Due to incomplete backcrossing, the genome of B1.RIII mice contains RIII-derived regions outside of H-2. One of these ‘contaminating’ regions, Cia8 on chromosome 10, was previously shown to control the development of collagen antibody induced arthritis. The goal of this study was to genetically interrogate the role of Cia8 and H-2 in IL-23 minicircle-induced murine spondyloarthritis. Methods: Informative crosses were set up between B1.RIII (Cia8r/r.H-2r/r) and B10 (Cia8b/b.H-2b/b) mice and between B1.RIII and B6 (Cia8b/b.H-2b/b) mice, respectively. Genotyped adult male littermates were hydrodynamically injected with 50 ng IL-23 EEV (System Bioscience) and blindly monitored for the development of arthritis every other day for 2 weeks. At the end of the study, IL-23 was measured in the serum and forepaws were analyzed by light microscopy. Results: In the offspring from a (B1.RIII × B10) N2 intercross, Cia8r/r.H-2r/r and Cia8b/b.H-2r/r mice developed arthritis with similar incidence and severity whereas Cia8r/r.H2b/b mice did not develop arthritis. In (B1.RIII × B6) F2 mice, H-2b/b mice were similarly protected while H-2r/r and H-2b/r mice developed arthritis. The Cia8 genotype (Cia8r/r vs. Cia8b/b) had no impact on arthritis development in (B1.RIII × B6) F2 mice. Serum IL-23 levels were comparable between groups. Conclusions: The development of IL-23 induced murine spondyloarthritis is controlled by the genomic background of the mice. Data from two complementary experiments demonstrate that arthritis susceptibility in this model maps to the H-2 (MHC) region on chromosome 17 and not Cia8 on chromosome 1. The critical role of the MHC in IL-23 minicircle-induced arthritis is surprising, considering that gd T cells are not MHC restricted. IL-23 minicircle-induced arthritis may serve as a model to interrogate the relationship between MHC and the IL-23/IL-17A axis. Platelet activation is present in psoriasis and associated with biomarkers of inflammation and vascular stiffness Kamelia Drenkova, Khrystyna Myndzar, Stuart D Katz, Andrea Neimann, Jose U Scher, James Krueger, Jeffrey S Berger, and Michael Garshick NYU Langone Health, New York, NY, USA New York University School of Medicine, New York, NY, USA The Rockefeller University, New York, NY, USA NYU Langone Medical Center, New York, NY, USA 100 Journal of Psoriasis and Psoriatic Art