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

Authors

  • Qiong Wu,

    1. Rheumatology Unit, UCL Institute of Child Health, University College London, London, UK
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    • The authors made equal contributions.
  • Anne M. Pesenacker,

    Corresponding author
    1. Rheumatology Unit, UCL Institute of Child Health, University College London, London, UK
    Current affiliation:
    1. Department of Surgery, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
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    • The authors made equal contributions.
  • Alka Stansfield,

    1. Scientific Research Laboratory, Cell Medica, London, UK
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  • Douglas King,

    1. Division of Infection and Immunity, Department of Immunology, University College, London, UK
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  • Dawn Barge,

    1. Department of Paediatric Immunology, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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  • Helen E. Foster,

    1. Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, and Great North Children's Hospital, London, UK
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  • Mario Abinun,

    1. Department of Paediatric Immunology, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
    2. Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, and Great North Children's Hospital, London, UK
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  • Lucy R. Wedderburn

    1. Rheumatology Unit, UCL Institute of Child Health, University College London, London, UK
    2. Arthritis Research UK Centre for Adolescent Rheumatology, University College, London, UK
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Summary

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 β 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 11·5 years), four patients remain in complete remission, while one child 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 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.

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