Derivation of a Multivariable Psoriatic Arthritis Risk Estimation Tool (PRESTO): A Step Towards Prevention.

OBJECTIVE: A simple, scalable tool that identifies psoriasis patients at high risk for developing psoriatic arthritis (PsA) could improve early diagnosis. We aimed to develop a risk prediction model for the development of PsA and to assess its performance among patients with psoriasis. METHODS: We analyzed data from a prospective cohort of psoriasis patients without PsA at enrollment. Participants were assessed annually by a rheumatologist for the development of PsA. Information about their demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms was used to develop prediction models for PsA. Penalized binary regression models were used for variable selection while adjusting for psoriasis duration. Risks of developing PsA over 1- and 5-year time periods were estimated. Model performance was assessed by the area under the curve (AUC) and calibration plots. RESULTS: Among 635 psoriasis patients, 51 and 71 developed PsA during the 1-year and 5-year follow-up periods, respectively. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (AUC 72.3). The risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesion, psoriasis severity, fatigue, pain, and use of systemic nonbiologic medication or phototherapy (AUC 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities. CONCLUSIONS: The development of PsA within clinically meaningful time frames can be predicted with reasonable accuracy for psoriasis patients using readily available clinical variables.

Sportomics method to assess acute phase proteins in Olympic level athletes using dried blood spots and multiplex assay.

Sportomics is a subject-centered holistic method similar to metabolomics focusing on sports as the metabolic challenge. Dried blood spot is emerging as a technique due to its simplicity and reproducibility. In addition, mass spectrometry and integrative computational biology enhance our ability to understand exercise-induced modifications. We studied inflammatory blood proteins (Alpha-1-acid glycoprotein-A1AG1; Albumin; Cystatin C; C-reactive protein-CRP; Hemoglobin-HBA; Haptoglobin-HPT; Insulin-like growth factor 1; Lipopolysaccharide binding protein-LBP; Mannose-binding lectin-MBL2; Myeloperoxidase-PERM and Serum amyloid A1-SAA1), in 687 samples from 97 World-class and Olympic athletes across 16 sports in nine states. Data were analyzed with Spearman's rank-order correlation. Major correlations with CRP, LBP; MBL2; A1AG1, and SAA1 were found. The pairs CRP-SAA1 and CRP-LBP appeared with a robust positive correlation. Other pairs, LBP-SAA1; A1AG1-CRP; A1AG1-SAA1; A1AG1-MBL, and A1AG1-LBP, showed a broader correlation across the sports. The protein-protein interaction map revealed 1500 interactions with 44 core proteins, 30 of them linked to immune system processing. We propose that the inflammation follow-up in exercise can provide knowledge for internal cargo management in training, competition, recovery, doping control, and a deeper understanding of health and disease.

Consensus terminology for preclinical phases of psoriatic arthritis for use in research studies: results from a Delphi consensus study.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.

Rho-GTPase pathways may differentiate treatment response to TNF-alpha and IL-17A inhibitors in psoriatic arthritis.

Biological therapies have dramatically improved the therapeutic landscape of psoriatic arthritis (PsA); however, 40-50% of patients are primary non-responders with response rates declining significantly with each successive biological therapy. Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent selection of biologic agents. We interrogated 40 PsA patients initiating either tumour necrosis factor inhibitors (TNFi) or interleukin-17A inhibitors (17Ai) for active PsA. Patients achieving low disease activity according to the Disease Activity Index for PsA (DAPSA) at 3 months were classified as responders. Baseline and 3-month CD4+ transcript profiling were performed, and novel signaling pathways were identified using a multi-omics profiling and integrative computational analysis approach. Using transcriptomic data at initiation of therapy, we identified over 100 differentially expressed genes (DEGs) that differentiated IL-17Ai response from non-response and TNFi response from non-response. Integration of cell-type-specific DEGs with protein-protein interactions and further comprehensive pathway enrichment analysis revealed several pathways. Rho GTPase signaling pathway exhibited a strong signal specific to IL-17Ai response and the genes, RAC1 and ROCKs, are supported by results from prior research. Our detailed network and pathway analyses have identified the rewiring of Rho GTPase pathways as potential markers of response to IL17Ai but not TNFi. These results need further verification.

Complexities in Genetics of Psoriatic Arthritis.

PURPOSE OF THE REVIEW: To provide a general overview and current challenges regarding the genetics of psoriatic disease. With the use of integrative medicine, multiple candidate loci identified to date in psoriatic disease will be annotated, summarized, and visualized. Recent studies reporting differences in genetic architecture between psoriatic arthritis and cutaneous-only psoriasis will be highlighted. RECENT FINDINGS: Focusing on functional pathways that connect previously identified genetic variants can increase our understanding of psoriatic diseases. The genetic architecture differs between psoriatic arthritis and cutaneous-only psoriasis with arthritis-specific signals in linkage disequilibrium independent of the published psoriasis signals. Integrative medicine is helpful in understanding cellular mechanisms of psoriatic diseases. Careful selection of the psoriatic disease cohort has translated into mechanistic differences among psoriatic arthritis and cutaneous psoriasis.

Proteinases and their receptors in inflammatory arthritis: an overview.

Proteinases are enzymes with established roles in physiological and pathological processes such as digestion and the homeostasis, destruction and repair of tissues. Over the past few years, the hormone-like properties of circulating proteinases have become increasingly appreciated. Some proteolytic enzymes trigger cell signalling via proteinase-activated receptors, a family of G protein-coupled receptors that have been implicated in inflammation and pain in inflammatory arthritis. Proteinases can also regulate ion flux owing to the cross-sensitization of transient receptor potential cation channel subfamily V members 1 and 4, which are associated with mechanosensing and pain. In this Review, the idea that proteinases have the potential to orchestrate inflammatory signals by interacting with receptors on cells within the synovial microenvironment of an inflamed joint is revisited in three arthritic diseases: osteoarthritis, spondyloarthritis and rheumatoid arthritis. Unanswered questions are highlighted and the therapeutic potential of modulating this proteinase-receptor axis for the management of disease in patients with these types of arthritis is also discussed.

Synovial fluid proteomics in the pursuit of arthritis mediators: An evolving field of novel biomarker discovery.

Synovial fluid (SF) is a protein-rich fluid produced into the joint cavity by cells of the synovial membrane. Due to its direct contact with articular cartilage, surfaces of the bone, and the synoviocytes of the inner membrane, it provides a promising reflection of the biochemical state of the joint under varying physiological and pathophysiological conditions. This property of SF has been exploited within numerous studies in search of unique biomarkers of joint pathologies with the ultimate goal of developing minimally invasive clinical assays to detect and/or monitor disease states. Several proteomic methodologies have been employed to mine the SF proteome. From elementary immunoassays to high-throughput analyses using mass spectrometry-based techniques, each has demonstrated distinct advantages and disadvantages in the identification and quantification of SF proteins. This review will explore the role of SF in the elucidation of the arthritis proteome and the extent to which high-throughput techniques have facilitated the discovery and validation of protein biomarkers from osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients.

Nonpharmacologic therapies in spondyloarthritis.

It is accepted that the optimal management of spondyloarthritis requires a combination of non-pharmacological and pharmacological interventions. Non-pharmacologic therapy in spondyloarthritis has generally focused on the exercise regimens whose purpose is to maintain mobility and strength, relieve symptoms, prevent or decrease spinal deformity, contribute to long-term cardiopulmonary health, and improve overall function and quality of life. Exercise programs such as home exercise, group exercise, inpatient programs, and spa exercise have all been the subject of multiple reports that are reviewed here. Studies reviewed support the use of exercise, spa therapy, manual therapy, and electrotherapeutic modalities. Additional topics that are finding relevance in spondyloarthritis are the behavioral interventions that maximize knowledge, motivation for compliance, and healthy lifestyle choices including smoking cessation, weight management, diet, and probiotics. However, the quality and generalizability of the studies are limited.