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1.
Ann Rheum Dis ; 78(8): 1107-1113, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31005900

RESUMO

OBJECTIVES: 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. The proposed biphasic model of SJIA also implies a 'window of opportunity' to abrogate the development of chronic arthritis. We aimed to identify novel SJIA biomarkers during different disease phases. METHODS: Children with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA syst ) or polyarticular disease (SJIA poly ). A discovery cohort of n=10 patients per SJIA group, plus n=10 with infection, was subjected to unbiased label-free liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay screens. In a separate verification cohort (SJIA syst , n=45; SJIA poly , n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays. RESULTS: Signatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA syst from SJIA poly well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA syst vs SJIA poly ) and 77% (SJIA syst vs infection) of all cases. CONCLUSIONS: Molecular signatures differentiating two phenotypes of SJIA were identified suggesting shifts in underlying immunological processes in this biphasic disease. Biomarker signatures separating SJIA in its initial autoinflammatory phase from the main differential diagnosis (ie, infection) could aid early-stage diagnostic decisions, while markers of a phenotype switch could inform treat-to-target strategies.

2.
Curr Rheumatol Rep ; 20(9): 53, 2018 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-30008153

RESUMO

PURPOSE OF REVIEW: 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 disease activity. RECENT FINDINGS: Mass spectrometry and affinity proteomic methodologies have been used to identify biomarker panels in synovial fluid, serum, plasma, or urine of pediatric and adult chronic arthritis patients. Notably, despite the numerous efforts to develop new and better biomarker panels, very few have undergone extensive analytical and clinical validation and been adopted into routine use for patient benefit. There remains a significant gap between discovery of chronic arthritis biomarker signatures and their validation for clinical use.


Assuntos
Artrite/diagnóstico , Biomarcadores/análise , Proteômica/métodos , Doença Crônica , Humanos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes
3.
Clin Rev Allergy Immunol ; 55(3): 271-294, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28748366

RESUMO

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. Inherently irreversible and frequently progressive, the process of joint damage begins at, or before, the clinical onset of disease. Early recognition and intervention is thus crucial to patient outcome. At disease onset, however, PsA often resembles other forms of arthritis-especially rheumatoid arthritis (RA). Despite the similarities between PsA and RA, their distinctive pathologies require different treatments. For example, drugs that are effective in RA may not be effective in PsA and can even cause adverse effects. Since there is no currently validated test for PsA, the diagnosis is often missed or delayed and this has functional consequences for the patient. In the context of PsA and RA, making an accurate diagnosis is not the only challenge faced by rheumatologists. Choosing an effective and safe medication to manage the disease is another significant challenge and currently approximately 40% achieve meaningful responses such as minimal disease activity status. For the patient, several months may be lost as a result of trial and error testing-meanwhile, irreversible joint damage may occur. Clearly, more effective clinical tests are urgently needed to improve personalised patient care in PsA. Specifically, there is need to develop minimally invasive tests predictive of diagnosis, response to treatment and radiographic progression. In this review, we examined the biomarker development process, highlighted the importance of qualifying unmet clinical needs and emphasised the challenges that impede biomarker studies. We have compiled a comprehensive list of potentially clinically relevant biomarkers in PsA and provided a summary of proteomic technologies that might usefully support additional biomarker research in PsA.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Necessidades e Demandas de Serviços de Saúde , Artrite Psoriásica/etiologia , Artrite Psoriásica/terapia , Biomarcadores , Diagnóstico por Imagem , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Proteômica/métodos , Índice de Gravidade de Doença , Avaliação de Sintomas
4.
Proteomics Clin Appl ; 10(6): 691-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26332844

RESUMO

PURPOSE: 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. EXPERIMENTAL DESIGN: Serum samples from 32 patients (PsA; n = 16 and RA; n = 16) defined as active, early onset, and treatment naïve were analyzed using unbiased label-free LC-MS/MS, a microsphere bead-based immunoassay (Luminex xMAP) and an aptamer-based assay (SOMAscan). RESULTS: LC-MS/MS was used to quantify 324 proteins, while the Luminex xMAP targeted 48 proteins and SOMAscan supported the measurement of 1129 proteins. The combined data from these techniques gave reproducible quantification of 1501 proteins in total. Of these, 42 (LC-MS/MS), 3 (Luminex xMAP), and 127 (SOMAscan) proteins were found to be differentially expressed between PsA and RA (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Using three different and potentially complementary proteomic platforms we identified a total of 172 proteins that are differentially expressed in patients with PsA compared to RA. These proteins collectively represent candidates for inclusion in a protein signature that could be developed as a diagnostic test to discriminate patients with PsA from RA and therefore be of clinical utility.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Proteínas Sanguíneas/metabolismo , Adulto , Artrite Psoriásica/sangue , Artrite Psoriásica/patologia , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Biomarcadores/metabolismo , Cromatografia Líquida , Diagnóstico Diferencial , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem
5.
Clin Med (Lond) ; 15(6): 530-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26621940

RESUMO

The Royal College of Physicians' FallSafe care bundles constitute measures of good practice, some of which are recommended for all patients, some are additional measures for older and more vulnerable patients admitted to hospital, and there is another bundle for after an inpatient fall, to reduce the number of inpatient falls. In 2013 a dedicated healthcare assistant, trained by the falls team, started a monthly spot audit looking at preventative measures, on all inpatients on every ward of the trust. Monthly results were fed back to the ward managers, ward falls liaison nurses, doctors, therapists and pharmacy staff on each ward, to discuss at the monthly ward governance meetings. Training and advice on specific aspects of falls prevention were provided by falls nurse practitioners. In total, 9,679 patient episodes were recorded over the year. Compliance with the measures recommended by the FallSafe care bundles has improved following regular spot audit and training. This has led to an overall reduction in the number of inpatient falls. Despite this however, in the real world of changing patient demographics, ward closures and the increasing use of ambulatory care, the number of falls/1,000 bed days has increased.


Assuntos
Acidentes por Quedas/prevenção & controle , Pacotes de Assistência ao Paciente , Humanos , Pacientes Internados , Pacotes de Assistência ao Paciente/métodos , Pacotes de Assistência ao Paciente/normas , Pacotes de Assistência ao Paciente/estatística & dados numéricos , Segurança do Paciente , Médicos , Reino Unido
6.
Arthritis Res Ther ; 17: 141, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26028339

RESUMO

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. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Biomarcadores/análise , Progressão da Doença , Humanos , Articulações/patologia
7.
Curr Rheumatol Rep ; 17(5): 35, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25895652

RESUMO

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 tests to confirm if a patient has the disease or predict how they may respond to therapy. Instead, a range of classification criteria have been developed, and the experience of the treating clinician is heavily relied upon. It is therefore widely accepted that there is a significant and as yet unmet need for effective molecular markers in psoriatic arthritis. Protein mediators drive disease pathogenesis and, therefore, represent logical potential biomarkers. Indeed, significant advances have recently been made by the introduction of multiplexed protein biomarker tests for monitoring disease activity in rheumatoid arthritis. At the same time, recent advances in proteomics have enhanced the capabilities for the detection and discovery of protein biomarkers. These advances offer renewed opportunities for the development of multi-protein biomarker signatures to support clinical decision-making in the diagnosis, prognosis and treatment of psoriatic arthritis. This review summarises the pathogenesis of psoriatic arthritis, highlighting specific areas of unmet clinical need. Furthermore, it seeks to illustrate how the latest developments in proteomic technologies could be used to enhance our understanding of the molecular pathology of psoriatic arthritis and improve clinical outcomes and quality of life for patients.


Assuntos
Artrite Psoriásica/diagnóstico , Proteômica/métodos , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Humanos , Determinação de Necessidades de Cuidados de Saúde , Proteômica/tendências
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