David S Gibson

Ulster University · Biomedical Sciences Research Institute

Viral infections elicit anti-viral antibodies and have been associated with various chronic diseases. Detection of these antibodies can facilitate diagnosis, treatment of infection and understanding of the mechanisms of virus associated diseases. In this work, we assayed anti-viral antibodies using a novel high density-nucleic acid programmable pro...

Matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrometry (MS) is a powerful tool for both the qualitative and quantitative analysis of wide array of analytes. MALDI-TOF MS is simple, both in design and practice, and offers the advantages that analysis times are very short, the mass range is virtually unlimited, and sensiti...

Musculoskeletal diseases such as rheumatoid arthritis are complex multifactorial disorders that are chronic in nature and debilitating for patients. A number of drug families are available to clinicians to manage these disorders but few tests exist to target these to the most responsive patients. As a consequence, drug failure and switching to drug...

Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at t...

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic autoimmune diseases with variable clinical outcomes. We investigated whether the synovial fluid (SF) proteome could distinguish a subset of patients in whom disease extends to affect a large number of joints. SF samples from 57 patients were obtained around time of i...

Objectives: Predicting response to anti-tumour necrosis factor alpha (anti-TNFα) drugs at baseline remains an elusive goal in rheumatoid arthritis (RA) management. The purpose of this study was to determine if baseline genetic variants of PTPRC, AFF3, myD228, CHUK, MTHFR1, MTHFR2, CD226 and a number of KIR and HLA alleles could predict response to...

Rheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes—mostly occurring outside clinics—where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability,...

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1β plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The...

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin-(IL-) 1β plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The...

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has...

Osteoarthritis was previously thought of as 'wear and tear' as humans age, however there is increasing evidence to support an inflammatory theory. The NLRP3 inflammasome has been implicated in the pathogenesis of a number of arthritic disorders, producing proinflammatory cytokines and degradative enzymes such as IL-1β, TNF-α and MMP-3 which drive c...

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of...

Introduction: Management of co- and multi-morbidity continues to represent a major clinical challenge. There remains a lack of understanding of how multiple pathologies or conditions co-evolve or interact and importantly how treatments should be combined to effectively improve outcomes. This review highlights the challenges presented to the clinica...

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

Psoriatic arthritis is a form of inflammatory arthritis that is frequently associated with psoriasis. Individuals with this disease present with heterogeneous clinical manifestations, making it challenging to diagnose and select optimal treatment strategies. Perhaps, not unsurprisingly, there are currently no molecular diagnostic or prognostic test...

Musculoskeletal diseases such as rheumatoid arthritis are complex multifactorial disorders that are chronic in nature and debilitating for patients. A number of drug families are available to clinicians to manage these disorders, but few tests exist to target these to the most responsive patients. As a consequence, drug failure and switching to dru...

Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the acute respiratory distress syndrome (ARDS). In animal models of ARDS, keratinocyte growth factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown. Objectives:...

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet (n = 5) and one undergoing bariatric surgery (n = 7), used bot...

Background Killer cell immunoglobulin like receptors (KIR) expressed on NK and T cell subsets interact with HLA ligands to influence the reactivity of these cells. The KIR/HLA genotype of an individual can affect immune responses to infection and susceptibility to autoimmunity based on the number/type of genes present (1-3). Objectives The aim of t...

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

Background Juvenile idiopathic arthritis (JIA) is the one of the most common chronic childhood diseases with a prevalence of around 1/1000 [1]. Over time JIA can result in persistent joint inflammation leading to chronic pain and stiffness, joint deformity and damage. Disease aetiology remains unknown. Investigation of disease pathology at the leve...

Objective The objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis.Methods Fifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertro...

The milk of the one-humped camel (Camelus dromedarius) reportedly offers medicinal benefits, perhaps because of its unique bioactive components. Milk proteins were determined by (1) two-dimensional gel electrophoresis and peptide mass mapping and (2) liquid chromatography-tandem mass spectrometry (LC-MS/MS) following one-dimensional polyacrylamide...

Mass spectrometry is playing an increasingly important role in the characterization and quantification of peptides and proteins. In fact, more conventional approaches to characterization, including techniques such as Edman sequencing and amino acid (AA) analysis, have been largely displaced. Mass analysis — following either matrix-assisted laser de...

Supplementary materials.

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. A pilot study...

Table S1, a complete list of NAPPA proteins, presenting the Entrez gene symbol, protein name, cellular location and molecule type for each protein produced on the NAPPA array within the current study; Table S2, functional networks of NAPPA proteins, listing the physiological and pathological functions of 25 networks constructed from the constituent...

Figure S1, transcriptional regulation of antigen clusters, showing magnified sections of the hierarchical cluster analysis heatmap in Figure 3Ato illustrate two distinct clusters of 49 proteins targeted by antibodies within the plasma of study subjects. The proteins responsible for transcriptional regulation of the target antigens within cluster 1...

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 and discuss the issue of fitness for...

Despite the anticipated boom stemming from proteomic investigations, the rate at whichnovel protein biomarkers are introduced into clinical practice has remained static over thepast 20 years. The reality is that approaches to both discover and validate proteinbiomarkers remain inadequate, and consequently, many areas of medicine, including thebroad...

Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of inflammatory disorders, within which there are a number of clinical subgroups. Diagnosis and assignment to a particular subgroup can be problematical and more concise methods of subgroup classification are required. This study of the synovial membrane characterises the immunoh...

Cytokines are naturally occurring small regulatory proteins produced by variouscell types. They act as external controlling elements in haematopoiesis and also mediateand control immune and inflammatory responses. Changes in cytokine levels havebeen reported in chronic obstructive pulmonary disease (COPD), a common inflammatorydisease of the airway...

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 in whom inflammation extends to aff...

Current clinical, laboratory or radiological parameters cannot accurately diagnose or predict disease outcomes in a range of autoimmune disorders. Biomarkers which can diagnose at an earlier time point, predict outcome or help guide therapeutic strategies in autoimmune diseases could improve clinical management of this broad group of debilitating d...

Juvenile idiopathic arthritis reflects a group of clinically heterogeneous arthritides hallmarked by elevated concentrations of circulating immune complexes. In this study, the circulating immune complex proteome was examined to elucidate disease-associated proteins that are overexpressed in patients with an aggressive, and at times destructive, di...

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. The synovial fluid proteome at the time of...

This review aims to summarise our knowledge to date on the protein complement of the synovial fluid (SF). The tissues, structure and pathophysiology of the synovial joint are briefly described. The salient features of the SF proteome, how it is composed and the influence of arthritic disease are highlighted and discussed. The concentrations of prot...

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Fo...

Gastro-oesophageal reflux (GOR)-related aspiration is associated with respiratory disease, but the current "gold standard" investigation, the lipid-laden macrophage index (LLMI), is flawed. A specific marker of GOR-related aspiration should originate in the stomach, but not the lung. An assay to detect gastric pepsin in the bronchoalveolar lavage (...

The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-alpha can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-alpha-/- and wild-type (WT) control C57B6 neonatal mice by exposure to...

WE-14 is generated in subpopulations of chromogranin A immunopositive endocrine cells and neurons including those innervating the anterior uvea. This study investigated WE-14 in intact sclero-limbo-corneal tissue from embryonic (E17), neonatal (N0-N16), and adult mice using immunocytochemistry and confocal scanning laser microscopy. Weak WE-14 immu...

Early local invasion by astrocytoma cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine prote...

Introduction: Local tumour invasion gives rise to recurrence after surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Extracellular proteolytic enzymes including cysteine proteinases have been implicated in facilitating tumour cell invasion. The current study was designed to characterize the expression of the...

Difference in-gel electrophoresis (DIGE) is a recent adaptation of conventional two-dimensional gel electrophoresis (2-DE) that incorporates novel fluorescent labels, has multiplex attributes, and boasts software-assisted image analysis. Combined, these characteristics offer significant benefits in accuracy and reproducibility to quantify different...

Juvenile idiopathic arthritis (JIA) comprises a group of chronic, childhood onset, autoimmune diseases with variable clinical presentations, outcomes and therapeutic responses. It is known that joint damage may progress despite apparent decreased inflammatory activity by conventional laboratory and clinical assessments. The difference in outcome co...

Figure 3 - Multivariate analysis of proteins differentially expressed across patient subgroups Twenty two UK patients with juvenile idiopathic arthritis (JIA) according to ILAR criteria entered this preliminary study. There were 15 children with oligo-articular arthritis and 7 with RF-ve poly-articular arthritis. During a year follow up period, the...