Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis.

Abstract:

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. TRIAL REGISTRATION NUMBER:NCT01352858.

journal_name

Ann Rheum Dis

authors

Bell GM,Anderson AE,Diboll J,Reece R,Eltherington O,Harry RA,Fouweather T,MacDonald C,Chadwick T,McColl E,Dunn J,Dickinson AM,Hilkens CM,Isaacs JD

doi

10.1136/annrheumdis-2015-208456

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

227-234

issue

1

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2015-208456

journal_volume

76

pub_type

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