Development of a T-cell subset phenotyping, ready-to-use, flow cytometry kit for patients with rheumatoid arthritis

Project description

Background

Rheumatoid arthritis (RA) is the most prominent member of a vast number of immune mediated inflammatory diseases. It affects approximately 1-2% of the population, with no cure and >1 million patients having severe disability and reduced life expectancy.

A stepwise progression alongside the inflammatory arthritis continuum (IACon) of disease is clearly detectable clinically and is now a recognised concept, with a pre-clinical phase characterised by systemic autoimmunity (presence of anti-citrullinated peptide antibodies autoantibodies ACPA) but with no evidence of joint involvement; a phase of non-specific joint pain known as arthralgia, followed by the development of joint inflammation, which may or may not develop to RA. At this last stage, treatment is initiated.

This project will use previous flow cytometry data from panels that were developed to predict the progression alongside the IACon towards developing a novel kit that can be used by hospitals worldwide. Indeed, over the past 20 years, our group has demonstrated the potential of phenotyping CD4+T-cell as biomarkers for predicting patient’s progression alongside the IACon (references below). We have now reached the stage of these biomarkers being used to stratify patients in randomised clinical trials.

Aim

The project will progress around several objectives towards developing a routine test for rationalising the management of RA patients using stratification based on T-cell phenotyping biomarkers

• Objective 1: The Technical development of
  • a novel flow cytometry kit (based on wet or dry tube technology), in collaboration with BD UK
  • working with an industrial partner, establishing the basis for a centralised service for T-cell phenotyping using frozen blood samples for future international clinical trials
• Objective 2 : the Clinical validation/replication of findings  alongside the IACon
  • using the novel KIT comparing its performance to the current flow cytometry panel
  • working with clinician to validate further the clinical utility of the stratification strategies using T-cell phenotyping (internationally, via collaboration)
• Objective 3 : Develop SOPs for the use of the new Kit by hospital flow cytometry services as well as instruction for the analysis gating strategy with BD. 

All are important outcomes, both for millions of patients and their families but also to sustain a more rational and socioeconomic management of RA and for the future of rheumatology. 

Methods

Flow cytometry mainly, modelling of clinical outcome.

References

• L Hunt, EM Hensor, J Nam, A Burska, R Parmar, P Emery, F Ponchel. T-cell subsets: An immunological biomarker to predict progression to clinical arthritis in ACPA positive individuals. Annals Rheum Dis 2015, annrheumdis-2015 DOI. 10.1136/annrheumdis-2015-207991.
• F Ponchel, AN Burska, EA Hensor, R Raja, M Campbell, P Emery, PG Conaghan. Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthritis and Cartilage, 2015. 23 1870 -1878
• F Ponchel, V Goëb,R Parmar, Y El-Sherbiny, M Boissinot, J El Jawhari, A Burska, EM Vital, S Harrison, PG Conaghan, E Hensor,  P Emery,  An immunological biomarker to predict MTX response in early RA, Annals Rheum Dis. 2014;73(11):2047-53 doi: 10.1136/annrheumdis-2013-203566
• Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch MH, Verburg RJ, Henwood J, Douglas SH, Masurel A, Conaghan PG, Gesinde M, Taylor J, Markham AF, Emery P, van Laar JM, Isaacs JD. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood. 2002. 100, 4550-4556

Entry requirements

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. The ideal candidate will have an interest in clinical diagnostic and a background in cell biology and immunology, possibly with knowledge of flow cytometry.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0.
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to apply

To apply for this position potential applicants should initially contact the lead supervisor, Dr Frederique Ponchel directly.

Following this, please submit a formal application by completing a Faculty Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School.

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email.

If you have already applied for other positions, or any scholarships, using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email to inform us you would like to be considered for this scholarship project.