ePrints

Immunological characteristics and T-cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T-cell-depleted autologous stem cell transplantation

Lookup NU author(s): Emerita Professor Helen Foster, Dr Mario Abinun

Downloads

• Published version [.pdf]

Licence

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

Children with systemic Juvenile Idiopathic Arthritis (sJIA), the most severe subtype of JIA, are at risk 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 after ASCT is unknown. Immune reconstitution of T cells, B cells, natural killer cells, natural killer T cells and monocytes, in parallel with T-cell receptor (TCR) diversity by analysis of the variable region (TCRVb) complementarity determining region-3 (CDR3) using spectratyping and sequencing, were studied in five children with sJIA before and after ASCT. At time of follow up (mean 11 center dot 5years), four patients remain in complete remission, while one child relapsed within 1month 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 after transplant in certain TCRVb families. Further, re-emergence of pre-ASCT clonal sequences in addition to new sequences was identified after 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.

Publication metadata

Author(s): Wu Q, Pesenacker AM, Stansfield A, King D, Barge D, Foster HE, Abinun M, Wedderburn LR

Publication type: Article

Publication status: Published

Journal: Immunology

Year: 2014

Volume: 142

Issue: 2

Pages: 227-236

Print publication date: 01/06/2014

Online publication date: 24/04/2014

Acceptance date: 05/01/2014

Date deposited: 01/10/2014

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/imm.12245

DOI: 10.1111/imm.12245

Altmetrics

Funding

Share