Publications

Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent...

Differentiating patients with psoriasis from psoriatic arthritis using collagen biomarkers.

Around 30% of patients diagnosed with cutaneous psoriasis (PsC) will go on to develop psoriatic arthritis (PsA) which includes inflammation of the joints. Collagens are core proteins in all tissues, which are involved in the inflammatory process in both PsC and PsA. The aim of this study is to investigate collagen biomarkers and their potential use in separating the three patient groupings: PsC, PsA and healthy donors...

HIPPOCRATES: improving diagnosis and outcomes in psoriatic arthritis.

Combining the diverse expertise of clinical and scientific researchers from across Europe as well as patient representatives and pharmaceutical industry partners, the HIPPOCRATES consortium aims to characterize the molecular pathways underlying psoriatic arthritis in order to improve early diagnosis and precision treatment strategies for the disease...

Basic Science Session 1. Biomarkers for Psoriatic Arthritis Treatment Response and Joint Damage Progression: An Update on 2 Industry-GRAPPA Projects.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has identified several priority areas for biomarker development, including biomarkers to predict at baseline which patients may progress to develop joint damage and whether a patient will respond to a specific targeted therapy...

Identification and Evaluation of Serum Protein Biomarkers That Differentiate Psoriatic Arthritis From Rheumatoid Arthritis

The objective of this study was to identify serum protein biomarkers that might distinguish patients with early inflammatory arthritis (IA) with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA), which may be used to support appropriate early intervention…

Standardized Workflow for Precise Mid- and High-Throughput Proteomics of Blood Biofluids.

Accurate discovery assay workflows are critical for identifying authentic circulating protein biomarkers in diverse blood matrices. Maximizing the commonalities in the proteomic workflows between different biofluids simplifies the approach and increases the likelihood for reproducibility. We developed a workflow that can accommodate 3 blood-based proteomes: naive plasma, depleted plasma and dried blood...

Early Origins of Psoriatic Arthritis: Clinical, Genetic and Molecular Biomarkers of Progression From Psoriasis to Psoriatic Arthritis.

Greater than 90% of patients with psoriatic arthritis (PsA) first develop their arthritis on a background of known psoriasis (Pso). Thus, having skin/nail Pso certainly is an important risk factor for PsA but as PsA develops in <30% of those affected with Pso, the presence of Pso alone is insufficient as a means of identifying which patients with Pso will develop PsA...

A high-stringency blueprint of the human proteome.

The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome...

Applying precision medicine to unmet clinical needs in psoriatic disease.

Psoriatic disease (PsD) is a heterogeneous condition that can affect peripheral and axial joints (arthritis), entheses, skin (psoriasis) and other structures. Over the past decade, considerable advances have been made both in our understanding of the pathogenesis of PsD and in the treatment of its diverse manifestations. However, several major areas of continued unmet need in the care of patients with PsD have been identified...

Aiming for Cure and Preventive Initiatives in Psoriatic Disease: Building Synergy at NPF, GRAPPA, and PPACMAN.

To provide a general overview of the organizations dedicated to advance clinical and translational research in the field of psoriatic disease and to describe the current and future opportunities for team science approaches to overcome unmet needs in the field. Descriptions of initiatives from the NPF, PPACMAN, and GRAPPA are summarized...

Moving Toward Precision Medicine in Psoriasis and Psoriatic Arthritis.

Current management approaches for the treatment of psoriasis and psoriatic arthritis (PsA) are imprecise and depend largely on clinical assessment. A more precise approach, which takes into account an individual patient’s variations in genes, proteins, environment, and lifestyle, is beginning to receive attention with the most advanced progress seen in the treatment of cancer...

Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis.

The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease...

Advancing research paradigms and pathophysiological pathways in psoriatic arthritis and ankylosing spondylitis: Proceedings of the 2017 Platform for the Exchange of Expertise and Research (PEER) meeting.

The seronegative spondyloarthropathies, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are characterized by varied clinical symptoms, severity, and disease course. Diagnosis and monitoring can be challenging because there is no definitive laboratory biomarker...

Proteomics in Chronic Arthritis-Will We Finally Have Useful Biomarkers?

Current technical advances enable the assessment of the complex changes in body fluid proteomes and thus allow for the discovery of biomarker signatures rather than just following differences of a single marker. In this review, we aim to summarize current approaches to discover and evaluate multi-biomarker panels for improved monitoring of chronic arthritis...

Bayesian Additive Regression Trees using Bayesian Model Averaging.

Bayesian Additive Regression Trees (BART) is a statistical sum of trees model. It can be considered a Bayesian version of machine learning tree ensemble methods where the individual trees are the base learners. However, for datasets where the number of variables p is large the algorithm can become inefficient and computationally expensive...

Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet Clinical Needs.

Psoriatic arthritis (PsA) is a form of inflammatory arthritis (IA) affecting approximately 0.25% of the population. It is a heterogeneous disorder associated with joint damage, disability, disfiguring skin disease and in severe cases, premature mortality...

Clinical translation of MS-based, quantitative plasma proteomics: status, challenges, requirements, and potential.

Aided by the advent of advanced mass spectrometry (MS)-based technologies and methodologies, quantitative proteomics has emerged as a viable technique to capture meaningful data for candidate biomarker evaluation. To aid clinical translation, these methods generally utilize a bottom-up strategy with isotopically labeled standards and a targeted form of MS measurement...

Developing clinically relevant biomarkers in inflammatory arthritis: A multiplatform approach for serum candidate protein discovery.

To identify candidate biomarkers that have the potential to distinguish between patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) and explore the value of combining different protein discovery platforms for the development of a multiplexed protein biomarker panel...

A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumor necrosis factor alpha, interleukins (IL)-17 and IL-23. Although 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy...

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease...

Discovery and confirmation of a protein biomarker panel with potential to predict response to biological therapy in psoriatic arthritis.

Biological therapies, which include antitumour necrosis factor-α and T-cell inhibitors, are potentially effective treatments for psoriatic arthritis (PsA) but are costly and may induce a number of side effects. Response to treatment in PsA is variable and difficult to predict. Here, we sought to identify a panel of protein biomarkers...

Why have so few proteomic biomarkers "survived" validation? (Sample size and independent validation considerations).

Proteomic biomarker discovery has led to the identification of numerous potential candidates for disease diagnosis, prognosis, and prediction of response to therapy. However, very few of these identified candidate biomarkers reach clinical validation and go on to be routinely used in clinical practice...

Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease.

Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1,000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown...

Biomarkers in rheumatology, now and in the future.

This review examines the biomarker development process by using rheumatic disorders as the disease model for discussion. We evaluate the current role of biomarkers in the practice of rheumatology and discuss their likely role in the future. We define the essential components of the biomarker development pipeline...

Stratification and monitoring of juvenile idiopathic arthritis patients by synovial proteome analysis.

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish patients...

Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis – Proteomic patterns of joint inflammation in early stage disease

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples...