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Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis

Lookup NU author(s): Dr Gillian Bell, Dr Amy AndersonORCiD, Julie Diboll, Oliver Eltherington, Dr Rachel Harry, Tony Fouweather, Dr Thomas Chadwick, Emerita Professor Elaine McCollORCiD, Janice Dunn, Professor Anne Dickinson, Professor Catharien Hilkens, Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objectives To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities.Methods An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.Results There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.Conclusion IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable.

Publication metadata

Author(s): Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, Fouweather T, MacDonald C, Chadwick T, McColl EM, Dunn J, Dickinson AM, Hilkens CMU, Isaacs JD

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2017

Volume: 76

Issue: 1

Pages: 227-234

Print publication date: 01/01/2017

Online publication date: 26/04/2016

Acceptance date: 24/03/2016

Date deposited: 23/05/2016

ISSN (print): 0003-4967

ISSN (electronic): 2056-5933

Publisher: BMJ Publishing Group


DOI: 10.1136/annrheumdis-2015-208456

PubMed id: 27117700


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Funder referenceFunder name
National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust
Newcastle University
18155Arthritis Research UK
BM1305European Cooperation for Science and Technology Action to Focus and Accelerate Cellular Tolerance-inducing Therapies (A FACTT)
18155VERSUS Arthritis (formerly Arthritis Research UK)