Wu, Q;
Pesenacker, AM;
Stansfield, A;
King, D;
Barge, D;
Foster, HE;
Abinun, M;
(2014)
Immunological characteristics and T cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T cell depleted autologous stem cell transplantation.
Immunology
, 142
(2)
pp. 227-236.
10.1111/imm.12245.
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Abstract
Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk of from destructive polyarthritis and growth failure, and corticosteroids as part of conventional treatment can result in osteoporosis and growth delay. In children where there is failure or toxicity from drug therapies, disease has been successfully controlled by T cell depleted autologous stem cell transplantation (ASCT). At present, the immunological basis underlying remission post ASCT is unknown. Immune reconstitution of T, B, NK, NK-T cell and monocytes, in parallel with T cell receptor diversity by analysis of beta variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in 5 children with sJIA before and after ASCT. At time of follow up (mean 11.5 years), 4 patients remain in complete remission, while 1 child had relapsed within 1 month of transplant. The CD8(+) TCRVb repertoire was highly oligoclonal early in immune reconstitution and re-emergence of pre-transplant TCRVb CDR3 dominant peaks was observed post transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified post transplant. These results suggest that a chimeric TCR repertoire, comprising T cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Immunological characteristics and T cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T cell depleted autologous stem cell transplantation. |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/imm.12245 |
| Publisher version: | http://dx.doi.org/10.1111/imm.12245 |
| Additional information: | © 2014 The Authors. Immunology published by John Wiley & Sons Ltd. Immunology, 142, 227–236 227 This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | Autologous Stem Cell Transplantation, Childhood Arthritis, Immune reconstitution, T cell receptor repertoire clonal diversity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1420642 |
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