Dr Arthur Pratt
Intermediate Clinical Fellow, Honorary Consulatant Rheumatologist
- Email: email@example.com
- Telephone: +44 (0) 191 208 5462
- Address: Floor 3, William Leech Building,
The Medical School,
Framlington Place, Newcastle,
Dr. Arthur G Pratt - BSc, MBChB, MRCP, PhD
Arthur completed his medical training at Leeds Medical School in 2001, with an intercalated BSc degree in Molecular Medicine. After admission to the Royal College of Physicians in 2004 he was awarded an Arthritis Research UK Research Training Fellowship in 2007, having moved to the Newcastle to establish the Northeast Early Arthritis Cohort, and he completed his doctoral studies in 2011. Following a spell as NHIR Clinical Lecturer in Rheumatology, he currently works as an Intermediate Clinical Fellow at Newcastle University. His time is divided between NHS work as an Honorary Consultant Rheumatologist (running the early arthritis service at The Freeman Hospital), clinical trial work, and research (including PhD student supervision) within the Institute of Cellular Medicine.
I am interested in how an improved understanding of the aetiopathogenesis of early rheumatoid arthritis (RA) might improve our ability to diagnose and treat patients with the disease. My research seeks to identify molecular biomarkers that begin to stratify this highly heterogeneous condition into subgroups of clinical significance.
Rheumatoid arthritis is a chronic and highly heterogeneous disease of immune dysregulation characterised by painful and destructive inflammation of synovial joints. Despite a wealth of existing and emerging therapies there is no cure for the condition, which remains a cause of disability, reduced quality of life and increased mortality. An overarching aim in our laboratory is to develop biomarkers that stratify patients according to pathobiology during the earliest clinical stage of RA, potentially enabling more rational therapeutic targeting.
We have developed a well characterised early arthritis inception cohort which has provided a rich resource for observational studies. Genetic investigations increasingly emphasise an orchestrating role for CD4 and B lymphocytes in RA pathogenesis, and our work to date has focused on these cell types: for example, our recent expression quantitative trait locus (eQTL) analysis of CD4 lymphocytes in untreated arthritis patients refined the candidate causal gene landscape of RA. The transcriptome of these cells also points to the importance of interleukin-6 mediated STAT3 signalling as an early event in a diagnostically challenging RA sub-group, and we have validated this finding and continue to investigate its potential implications for the clinic.
Finally, we are increasingly interested in delineating mechanisms of immune dysregulation that are shared between diseases beyond RA, and the opportunities they may afford to re-purpose RA drugs in other conditions and vice versa.
- Anderson AE, Maney NJ, Nair N, Lendrem DW, Skelton AJ, Diboll J, Brown PM, Smith GR, Carmody RJ, Barton A, Isaacs JD, Pratt AG. Expression of STAT3-regulated genes in circulating CD4+ T cells discriminates rheumatoid arthritis independently of clinical parameters in early arthritis. Rheumatology (Oxford) 2019, Epub ahead of print.
- Wood MJ, Leckenby A, Reynolds G, Spiering R, Pratt AG, Rankin KS, Isaacs JD, Haniffa MA, Milling S, Hilkens CM. Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients. JCI Insight 2019, 4(2), e125325.
- Iqbal K, Lendrem DW, Hargreaves B, Isaacs JD, Thompson B, Pratt AG. Routine musculoskeletal ultrasound findings impact diagnostic decisions maximally in autoantibody-seronegative early arthritis patients. Rheumatology 2019, Epub ahead of print.
- Thalayasingam N, Nair N, Skelton AJ, Massey J, Anderson AE, Clark AD, Diboll J, Lendrem DW, Reynard LN, Cordell HJ, Eyre S, Isaacs JD, Barton A, Pratt AG. CD4+ and B lymphocyte expression quantitative traits at rheumatoid arthritis risk loci in untreated early arthritis: implications for causal gene identification. Arthritis and Rheumatology 2018, 70(3), 361-370.
- Just SA, Humby F, Lindegaard H, De Bellefon LM, Durez P, Vieira-Sousa E, Teixeira R, Stoenoiu M, Werlinrud J, Rosmark S, Larsen PV, Pratt A, Choy E, Gendi N, Buch MH, Edwards CJ, Taylor PC, McInnes IB, Fonseca JE, Pitzalis C, Filer A. Patient-reported outcomes and safety in patients undergoing synovial biopsy: Comparison of ultrasound-guided needle biopsy, ultrasound-guided portal and forceps and arthroscopic-guided synovial biopsy techniques in five centres across Europe. RMD Open 2018, 4(2), e000799.
- Cooles FAH, Anderson AE, Skelton A, Pratt AG, Kurowska-Stolarska MS, McInnes I, Hilkens CMU, Isaacs JD. Phenotypic and transcriptomic analysis of peripheral blood plasmacytoid and conventional dendritic cells in early drug naïve rheumatoid arthritis. Frontiers in Immunology 2018, 9, 755.
- Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis?. Current Opinion in Rheumatology 2018, 30(2), 207-214.
- Pollock J, Raza K, Pratt AG, Hanson H, Siebert S, Filer A, Isaacs JD, Buckley CD, Mcinnes IB, Falahee M. Patient and researcher perspectives on facilitating patient and public involvement in rheumatology research. Musculoskeletal Care 2017, 15(4), 395-399.
- Baker KF, Pratt AG, Thompson B, Isaacs JD. Response to: 'Let's stop fooling ourselves. In RA, only ACR/EULAR criteria define remission and equate with absence of disease!' by Boers. Annals of the Rheumatic Diseases 2017, 76(6), e12.
- Orr C, Sousa E, Boyle DL, Buch MH, Buckley CD, Canete JD, Catrina AI, Choy EHS, Emery P, Fearon U, Filer A, Gerlag D, Humby F, Isaacs JD, Just SoA, Lauwerys BR, Le Goff B, Manzo A, McGarry T, McInnes IB, Najm A, Pitzalis C, Pratt A, Smith M, Tak PP, Thurlings R, Fonseca JE, Veale DJ. Synovial tissue research: A state-of-the-art review. Nature Reviews Rheumatology 2017, 13(8), 463-475.
- Cooles FAH, Anderson AE, Lendrem DW, Norris J, Pratt AG, Hilkens CMU, Isaacs JD. The interferon gene signature is increased in patients with early treatment-naive rheumatoid arthritis and predicts a poorer response to initial therapy. Journal of Allergy and Clinical Immunology 2017, 141(1), 445-448.e4.
- Anderson AE, Swan DJ, Wong OY, Buck M, Eltherington O, Harry RA, Patterson AM, Pratt AG, Reynolds G, Doran JP, Kirby JA, Isaacs JD, Hilkens CM. Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T-cells partly via TGF-β1. Clinical & Experimental Immunology 2017, 187(1), 113-123.
- Pratt AG, Anderson AE, Carmody RJ, Isaacs JD. Bcl-3 in CD4+ T Cell–Mediated Rheumatoid Arthritis Pathogenesis: Comment on the Article by Meguro et al. Arthritis and Rheumatology 2016, 68(3), 770-771.
- McGovern A, Schoenfelder S, Martin P, Massey J, Duffus K, Plant D, Yarwood A, Pratt AG, Anderson AE, Isaacs JD, Diboll J, Thalayasingam N, Ospelt C, Barton A, Worthington J, Fraser P, Eyre S, Orozco G. Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23. Genome Biology 2016, 17, 212.
- Pratt AG, Lendrem D, Hargreaves B, Aslam O, Galloway JB, Isaacs JD. Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data. Rheumatology 2016, 55(10), 1843-1848.
- Hanson H, Isaacs JD, Kay LJ, Lendrem DW, O'Brien N, Pratt AG, Rapley T. Experiences of staff and patients in relation to clinical research recruitment and involvement: a qualitative study. In: Rheumatology. 2016, Glasgow: Oxford University Press.
- Pratt AG, Massey J, Anderson AE, Nair N, Diboll J, Skelton A, Lendrem DW, Reynard LN, Cordell HJ, Eyre S, Barton A, Isaacs JD. Identification of novel expression quantitative trait loci in CD4+ T cells of untreated early arthritis patients. In: 36th European Workshop for Rheumatology Research. 2016, York: BMJ Group.
- Anderson AE, Pratt AG, Sedhom MA, Doran JP, Routledge C, Hargreaves B, Brown PB, LeCao KA, Isaacs JD, Thomas R. IL-6-driven STAT signalling in circulating CD4+ lymphocytes is a marker for early anti-citrullinated peptide antibody-negative rheumatoid arthritis. Annals of the Rheumatic Diseases 2016, 75, 466-473.
- Brown PM, Pratt AG, Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nature Reviews Rheumatology 2016, 12(12), 731-742.
- Reynolds G, Gibbon JR, Pratt AG, Coady D, Raftery G, Lorenzi AR, Gray A, Filer A, Buckley CD, Haniffa MA, Isaacs JD, Hilkens CM. Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis. Annals of the Rheumatic Diseases 2016, 75(5), 899-907.
- Baker KF, Thompson B, Lendrem DW, Pratt AG, Isaacs JD. Ultrasound measures of synovitis are independent of clinical parameters in the setting of rheumatoid arthritis remission: a cross-sectional analysis. In: 2016 Annual European Congress of Rheumatology. 2016, London, UK: BMJ Publishing Group.
- Pratt AG, Hargreaves B, Lendrem DW, Aslam O, Isaacs JD. Components of treatment delay in rheumatoid arthritis differ according to autoantibody status. In: 2015 ACR/ARHP Annual Meeting. 2015, San Francisco, CA, USA: John Wiley & Sons, Inc.
- Pratt AG, Isaacs JD. Genotyping in rheumatoid arthritis: a game changer in clinical management?. Expert Review of Clinical Immunology 2015, 11(3), 303-305.
- Pratt AG, Hargreaves B, Routledge C, Tiffin L, Norris J, Humphrey C, Isaacs JD. Reasons for Treatment Delay in Early Rheumatoid Arthritis Differ According to Autoantibody Status. In: Rheumatology 2015. 2015, Manchester, UK: Oxford University Press.
- Cooles FAH, Pratt AG, Lendrem DW, Ng WF, Aspray TJ, Isaacs JD. Retrospective analysis of the role of serum vitamin D in early rheumatic disease. Rheumatology 2015, 54(2), 374-375.
- Pratt AG, Anderson AE, Lendrem DW, Skelton A, Massey J, Nair N, Diboll J, Hargreaves B, Brown PM, Barton A, Isaacs JD. STAT3-regulated gene expression in circulating CD4+ T cells discriminates RA patients independently of clinical parameters in early arthritis: a validation study. In: 2015 ACR/ARHP Annual Meeting. 2015, San Francisco, CA.
- Pratt AG, Anderson AE, Nair N, Massey J, Diboll J, Skelton A, Hargreaves B, Routledge C, Lendrem D, Brown P, Barton A, Isaacs JD. The Importance of IL-6-STAT3 Mediated Activation of Circulating CD4+ T Cells in the Pathogenesis of Early Seronegative Rheumatoid Arthritis: A Validation Study. In: Rheumatology 2015. 2015, Manchester, UK: Oxford University Press.
- Anderson A, Routledge C, Isaacs J, Pratt A. Investigation of interleukin-6-driven STAT3 signalling in circulating lymphocytes of patients with early rheumatoid arthritis as a route to biomarker discovery. In: Spring Meeting for Clinician Scientists in Training. 2014, London, UK: Elsevier.
- Pratt AG, Isaacs JD. Seronegative rheumatoid arthritis: Pathogenetic and therapeutic aspects. Best Practice & Research Clinical Rheumatology 2014, 28(4), 651-659.
- Pratt AG, Brown PM, Cockell SJ, Wilson G, Isaacs JD. A CD4+T-Cell Gene Expression Signature Predicts Drug Survival on Methotrexate Monotherapy in Early Rheumatoid Arthritis. In: 33rd European Workshop for Rheumatology Research. 2013, Prague, Czech Republic: BMJ Publishing Group.
- Pratt AG, Lorenzi AR, Wilson G, Platt PN, Isaacs JD. Predicting persistent inflammatory arthritis amongst early arthritis clinic patients in the UK: is musculoskeletal ultrasound required?. Arthritis Research & Therapy 2013, 15(5), R118.
- Cooles FAH, Pratt AG, Ng WF, Aspray TJ, Isaacs JD. The Effect Of Vitamin D On Early Rheumatoid Arthritis: A Retrospective Cohort Analysis. In: ACR/ARHP Annual Meeting 2013. 2013, San Diego, CA, USA: Wiley-Blackwell.
- Pratt AG, Swan DC, Richardson S, Wilson G, Hilkens C, Young DA, Isaacs JD. A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly anti-citrullinated peptide antibody-negative disease. Annals of the Rheumatic Diseases 2012, 71(8), 1374-1381.
- Pratt AG, Brown PM, Cockell SJ, Wilson G, Isaacs JD. A CD4+T-Cell Gene Expression Signature Predicts Drug Survival On Methotrexate Monotherapy in Early Rheumatoid Arthritis. In: Annual Scientific Meeting of the American College of Rheumatology (ACR). 2012, Washington, DC, USA: John Wiley & Sons, Inc.
- Anderson AE, Lorenzi AR, Pratt A, Wooldridge T, Diboll J, Hilkens CM, Isaacs JD. Immunity 12 years after alemtuzumab in RA: CD5+ B-cell depletion, thymus-dependent T-cell reconstitution and normal vaccine responses. Rheumatology 2012, 51(8), 1397-1406.
- Burmester GR, Pratt AG, Scherer HU, van Laar JM. Rheumatoid arthritis: Pathogenesis and clinical aspects. In: Bijlsma, H, ed. EULAR Textbook on Rheumatic Diseases. London: BMJ Publications, 2012, pp.206-231.
- Cooles FAH, Pratt AG, Wilson G, Isaacs JD, Ng WF. Prevalence and diagnostic outcome relating to vitamin D deficiency in new patients presenting to an early arthritis clinic over 12 months. Clinical Rheumatology 2011, 30(8), 1137-1138.
- Pratt AG, Charles PJ, Chowdhury M, Wilson G, Venables PJ, Isaacs JD. Serotyping for an extended anti-citrullinated peptide autoantibody panel does not add value to CCP2 testing for diagnosing RA in an early undifferentiated arthritis cohort. Annals of the Rheumatic Diseases 2011, 70(11), 2056-2058.
- Tudhope SJ, von Delwig A, Falconer J, Pratt A, Woolridge T, Wilson G, Isaacs JD, Ng WF. Profound invariant natural killer T-cell deficiency in inflammatory arthritis. Annals of the Rheumatic Diseases 2010, 69(10), 1873-1879.
- Pratt AG, Isaacs JD, Mattey DL. Current concepts in the pathogenesis of early rheumatoid arthritis. Best Practice & Research: Clinical Rheumatology 2009, 23(1), 37-48.
- Pratt AG, Isaacs JD, Wilson G. The clinical utility of a rule for predicting rheumatoid arthritis in patients with early undifferentiated arthritis: comment on the article by van der Helm-van Mil et al. Arthritis & Rheumatism 2009, 60(3), 905.
- Lorenzi AR, Patterson AM, Pratt A, Jefferson M, Chapman CE, Ponchel F, Isaacs JD. Determination of thymic function directly from peripheral blood: a validated modification to an established method. Journal of Immunological Methods 2008, 339(2), 185-94.
- Pratt A, Nicholl K, Kay L. Comment on: Use of the QuantiFERON-TB® Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-α agents: The Newcastle (UK) experience: Reply . Rheumatology 2007, 46(12), 1864-1865.
- Marshall NJ, Pratt A, Kay LJ. Pamidronate infusions for Ankylosing Spondylitis give significant benefit to only a minority of patients. In: Rheumatology: Annual Meeting of the British Society of Rheumatology. 2007, Birmingham, UK: Oxford University Press.
- Pratt A, Nicholl K, Kay L. Use of the QuantiFERON TB Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-α agents: The Newcastle (UK) experience. Rheumatology 2007, 46(6), 1035-1036.