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  • Project No: #OxKEN-2021/4
  • Intake: OxKEN

PROJECT OVERVIEW

Patients with psoriatic disease (psoriasis and psoriatic arthritis) have a much higher risk of developing non-alcoholic liver disease. This is a difficult clinical problem as many disease-modifying drugs used for psoriasis and arthritis (e.g. methotrexate) may worsen the liver disease. Previously the only tests available for this have been liver function tests (often normal until the liver is quite damaged) or a liver biopsy (an invasive and risky procedure). LiverMultiScan is a novel, CE-marked and FDA-cleared product (Perspectum Diagnostics Ltd, UK https://perspectum-diagnostics.com/) that can non-invasively quantify liver tissue characteristics based on magnetic resonance imaging (MRI).

Our hypothesis is that this completely novel method of liver disease quantification using MRI LiverMultiScan technology can be applied in psoriatic disease allowing quantification and further understanding of this comorbidity.  The aims are to:

  • Quantify the true extent of liver disease in people with psoriatic disease compared to UK Biobank controls.
  • Investigate the causal pathological relationship between systemic inflammation, gut microbiome dysbiosis and liver disease in people with psoriatic disease
  • Explore the impact of commonly used psoriatic therapies such as methotrexate and biologics on liver inflammation and fibrosis.

The role of gut dysbiosis in psoriatic disease is becoming more evident but the potential impact of this dysbiosis on the liver, which is the first site of processing for microbial metabolites, has not yet been investigated. In particular, we plan to study a population of resident mucosal invariant T cells (MAIT) found in the liver which recognise microbial metabolites and are capable of producing pro-inflammatory type 17 cytokines such as IL-17A and F. MAIT cells have been associated with the pathogenesis of psoriatic disease and thus uniquely poised to link gut dysbiosis with Th17-driven joint inflammation.  The gut microbiome profile of individuals will be correlated with the MAIT cell transcriptomic signature.

Funding is already secured for a 100 patient cross-sectional study, across 2 UK centres, recruiting patients with psoriasis and PsA who are about to start disease-modifying therapy.  We will perform clinical assessments, LiverMultiScan MRI and collect blood/stool samples pre and post treatment.

KEYWORDS

Non-alcoholic fatty liver disease, psoriasis, psoriatic arthritis, imaging, MAIT cells.

TRAINING OPPORTUNITIES

FACS sorting, RNA sequencing, PCR, microbiome sampling, biostatistics, specialist psoriatic arthritis and combined rheum/derm clinics, presentations at national and international meetings,

KEY PUBLICATIONS

  1. MAIT Cells in Health and Disease. Provine NM, Klenerman P.Annu Rev Immunol. 2020 Apr 26;38:203-228. doi: 10.1146/annurev-immunol-080719-015428. Epub 2019 Jan 27.
  2. Cole S, Murray J, Simpson C, Okoye R, Tyson K, Griffiths M, Baeten D, Shaw S, Maroof A. Interleukin (IL)-12 and IL-18 Synergize to Promote MAIT Cell IL-17A and IL-17F Production Independently of IL-23 Signaling. Front Immunol. 2020 Nov 20;11:585134. doi: 10.3389/fimmu.2020.585134
  3. Coates Laura C, Moverley Anna R, McParland Lucy, Brown Sarah, Navarro-Coy Nuria, O’Dwyer John L, Meads David M, Emery Paul, Conaghan Philip G, Helliwell Philip S. (2015) Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet; 386(10012):2489-98.
  4. van Mens Leonieke JJ, van de Sande Marleen GH, van Kuijk Arno WR, Baeten Dominique, Coates Laura C. (2018) Ideal target for psoriatic arthritis? Comparison of remission and low disease activity states in a real-life cohort. Ann Rheum Dis;77(2):251-257.
  1. Coates LC, FitzGerald O, Merola JF, Smolen J, van Mens LJJ, Bertheussen H, Boehncke WH, Callis Duffin K, Campbell W, de Wit M, Gladman D, Gottlieb A, James J, Kavanaugh A, Kristensen LE, Kvien TK, Luger T, McHugh N, Mease P, Nash P, Ogdie A, Rosen CF, Strand V, Tillett W, Veale DJ, Helliwell PS. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis. Arthritis Rheumatol. 2018 Mar;70(3):345-355.

CONTACT INFORMATION OF ALL SUPERVISORS

Laura Coates

Paul Klenerman

Hussein Al-Mossawi