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Buchumschlag von Immunological characteristics and T‐cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T‐cell‐depleted autologous stem cell transplantation
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Immunological characteristics and T‐cell receptor clonal diversity in children with systemic juvenile idiopathic arthritis undergoing T‐cell‐depleted autologous stem cell transplan...

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Zeitschriftentitel: Immunology
Personen und Körperschaften: Wu, Qiong, Pesenacker, Anne M., Stansfield, Alka, King, Douglas, Barge, Dawn, Foster, Helen E., Abinun, Mario, Wedderburn, Lucy R.
In: Immunology, 142, 2014, 2, S. 227-236
Medientyp: E-Article
Sprache: Englisch
veröffentlicht:
Wiley
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Zusammenfassung: <jats:title>Summary</jats:title><jats:p>Children with systemic <jats:styled-content style="fixed-case">J</jats:styled-content>uvenile <jats:styled-content style="fixed-case">I</jats:styled-content>diopathic <jats:styled-content style="fixed-case">A</jats:styled-content>rthritis (s<jats:styled-content style="fixed-case">JIA</jats:styled-content>), the most severe subtype of <jats:styled-content style="fixed-case">JIA</jats:styled-content>, 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 <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell‐depleted autologous stem cell transplantation (<jats:styled-content style="fixed-case">ASCT</jats:styled-content>). At present, the immunological basis underlying remission after <jats:styled-content style="fixed-case">ASCT</jats:styled-content> is unknown. Immune reconstitution of <jats:styled-content style="fixed-case">T</jats:styled-content> cells, <jats:styled-content style="fixed-case">B</jats:styled-content> cells, natural killer cells, natural killer <jats:styled-content style="fixed-case">T</jats:styled-content> cells and monocytes, in parallel with <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell receptor (<jats:styled-content style="fixed-case">TCR</jats:styled-content>) diversity by analysis of the β variable region (<jats:styled-content style="fixed-case">TCRV</jats:styled-content>b) complementarity determining region‐3 (<jats:styled-content style="fixed-case">CDR</jats:styled-content>3) using spectratyping and sequencing, were studied in five children with s<jats:styled-content style="fixed-case">JIA</jats:styled-content> before and after <jats:styled-content style="fixed-case">ASCT</jats:styled-content>. 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 <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">TCRV</jats:styled-content>b repertoire was highly oligoclonal early in immune reconstitution and re‐emergence of pre‐transplant <jats:styled-content style="fixed-case">TCRV</jats:styled-content>b <jats:styled-content style="fixed-case">CDR</jats:styled-content>3 dominant peaks was observed after transplant in certain <jats:styled-content style="fixed-case">TCRV</jats:styled-content>b families. Further, re‐emergence of pre‐<jats:styled-content style="fixed-case">ASCT</jats:styled-content> clonal sequences in addition to new sequences was identified after transplant. These results suggest that a chimeric <jats:styled-content style="fixed-case">TCR</jats:styled-content> repertoire, comprising <jats:styled-content style="fixed-case">T</jats:styled-content>‐cell clones developed before and after transplant, can be associated with clinical remission from severe arthritis.</jats:p>
Umfang: 227-236
ISSN: 0019-2805
1365-2567
DOI: 10.1111/imm.12245