Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis

被引：251

作者：

Bell, G. M. ^{[1
]}

Anderson, A. E. ^{[1
]}

Diboll, J. ^{[1
]}

Reece, R. ^{[1
]}

Eltherington, O. ^{[1
]}

Harry, R. A. ^{[1
]}

Fouweather, T. ^{[2
]}

MacDonald, C. ^{[2
]}

Chadwick, T. ^{[2
]}

McColl, E. ^{[2
,3
]}

Dunn, J. ^{[4
]}

Dickinson, A. M. ^{[4
]}

Hilkens, C. M. U. ^{[1
]}

Isaacs, John D. ^{[1
]}

机构：

[1] Inst Cellular Med, Musculoskeletal Res Grp, Arthrit Res UK Rheumatoid Arthrit Pathogenesis Ct, Newcastle Upon Tyne, Tyne & Wear, England

[2] Newcastle Univ, Fac Med Sci, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England

[3] Newcastle Univ, Clin Trials Unit, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England

[4] Inst Cellular Med, Haematol Sci, Newcastle Upon Tyne, Tyne & Wear, England

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2017年 / 76卷 / 01期

关键词：

AUTOIMMUNITY; ANTIGEN; DISEASE;

D O I：

10.1136/annrheumdis-2015-208456

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 1x10(6), 3x10(6) or 10x10(6) 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 10x106 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 10x106 tolDC but no systemic clinical or immunomodulatory effects were detectable.

引用

页码：227 / 234

页数：8

共 24 条

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