Premium
Immunological characteristics and T ‐cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T ‐cell‐depleted autologous stem cell transplantation
Author(s) -
Wu Qiong,
Pesenacker Anne M.,
Stansfield Alka,
King Douglas,
Barge Dawn,
Foster Helen E.,
Abinun Mario,
Wedderburn Lucy R.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12245
Subject(s) - immunology , transplantation , t cell receptor , immune system , t cell , stem cell , polyarthritis , biology , complementarity determining region , medicine , arthritis , antibody , monoclonal antibody , genetics
Summary Children with systemic J uvenile I diopathic A rthritis (s JIA ), 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 ( TCRV b) complementarity determining region‐3 ( CDR 3) using spectratyping and sequencing, were studied in five children with s JIA 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 CD 8 + TCRV b repertoire was highly oligoclonal early in immune reconstitution and re‐emergence of pre‐transplant TCRV b CDR 3 dominant peaks was observed after transplant in certain TCRV b 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.